Radiation safety: a focus on lead aprons and thyroid shields in interventional pain management.

C-arm fluoroscopy is useful equipment in interventional pain management because it helps to guide correct needle targeting for the accurate injection and drug delivery. However, due to increased use of C-arm fluoroscopy in various pain procedures, the risk of radiation exposure is a significant concern for pain physicians. The harmful biological effects of ionizing radiation on the human body are well known. It is therefore necessary to strive to reduce radiation exposure. Lead aprons with thyroid shields are the most fundamental radiation protective devices for interventional procedures, and are very effective. However, the operator's radiation safety cannot be guaranteed because pain physicians seem to lack sufficient interest, knowledge, and awareness about radiation safety. Also, inappropriate care and use of radiation protective devices may result in a higher risk of radiation exposure. The purpose of this article was to review the literature on radiation safety with a focus on lead aprons and thyroid shields and present recommendations related to those devices during C-arm fluoroscopic-guided interventions by pain physicians.

GPCR Kinase (GRK)-2 Is a Key Negative Regulator of Itch: l-Glutamine Attenuates Itch via a Rapid Induction of GRK2 in an ERK-Dependent Way.

Many itch mediators activate GPCR and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by GPCR kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the link between GRKs and glutamine, an amino acid previously shown to be an itch reliever. Itch responses were evoked by histamine, chloroquine, and dinitrochlorobenzene-induced contact dermatitis (CD). Phosphorylation and protein expression were detected by immunofluorescent staining and Western blotting. GRK2 knockdown using small interfering RNA enhanced itch responses evoked by histamine, chloroquine, and dinitrochlorobenzene-induced CD, whereas GRK2 overexpression using GRK2-expressing adenovirus reduced the itch responses. Glutamine reduced all itch evoked by histamine, chloroquine, and dinitrochlorobenzene-induced CD. Glutamine-mediated inhibition of itch was abolished by GRK2 knockdown. Glutamine application resulted in a rapid and strong expression of GRK2 in not only dinitrochlorobenzene-induced CD (within 10 minutes) but also cultured rat dorsal root ganglion cells, F11 (within 1 minute). ERK inhibitor abrogates glutamine-mediated GRK2 expression and inhibition of itch in dinitrochlorobenzene-induced CD. Our data indicate that GRK2 is a key negative regulator of itch and that glutamine attenuates itch via a rapid induction of GRK2 in an ERK-dependent way.

FcγR/ROS/CK2α Is the Key Inducer of NF-κB Activation in a Murine Model of Asthma.

BACKGROUND: The transcription factor nuclear factor (NF)-κB plays a pivotal role in the development of allergic airway inflammation. However, the mechanism of NF-κB activation in asthma remains to be elucidated. METHODS: CK2α activation was assessed by CK2α phosphorylation and protein expression. Airway levels of histamine and cytokines were determined by ELISA. We used 2 (active and passive) forms of allergic pulmonary inflammation models. In the active form, the animals were immunized with ovalbumin (OVA) intraperitoneally, followed by an airway challenge with OVA. In the passive form, the animals were passively sensitized by intratracheal instillation with either anti-OVA IgE or anti-OVA IgG, followed by an airway challenge with OVA. The role of NADPH oxidase (NOX) in CK2α activation was assessed using NOX2-/- and NOX4-/- mice because NOX2 and NOX4 contribute to many inflammatory diseases. RESULTS: The second airway challenge increased CK2α phosphorylation and protein expression in airway epithelial cells as well as nuclear translocation of the p50 and p65 subunits of NF-κB, all of which were inhibited by the CK2α inhibitor 4,5,6,7-tetrabromobenzotriazole and the antioxidant N-acetyl-L-cysteine. CK2α phosphorylation and protein expression were significantly impaired in NOX2-/-, but not in NOX4-/-, mice. Induction of passive sensitization using anti-OVA IgE activated neither CK2α nor NF-κB. In contrast, induction of passive sensitization using anti-OVA IgG activated both CK2α and NF-κB. CONCLUSIONS: These data suggest that Fcγ receptor/reactive oxygen species/CK2α is a key inducer of NF-κB activation in airway epithelial cells in a murine model of asthma.

The radiation safety education and the pain physicians' efforts to reduce radiation exposure.

BACKGROUND: C-arm fluoroscopy equipment is important for interventional pain management and can cause radiation injury to physicians and patients. We compared radiation safety education and efforts to reduce the radiation exposure of pain specialists. METHODS: A survey of 49 pain specialists was conducted anonymously in 2016. The questionnaire had 16 questions. That questionnaire was about radiation safety knowledge and efforts to reduce exposure. We investigated the correlation between radiation safety education and efforts of radiation protection. We compared the results from 2016 and a published survey from 2011. RESULTS: According to the 2016 survey, all respondents used C-arm fluoroscopy in pain interventions. Nineteen respondents (39%) had received radiation safety education. Physicians had insufficient knowledge about radiation safety. When the radiation safety education group and the non-education group are compared, there was no significant difference in efforts to reduce radiation exposure and radiation safety knowledge. When the 2011 and 2016 surveys were compared, the use of low dose mode (P = 0.000) and pulsed mode had increased significantly (P = 0.001). The number checking for damage to radiation protective garments (P = 0.000) and use of the dosimeter had also increased significantly (P = 0.009). But there was no significant difference in other efforts to reduce radiation exposure. CONCLUSIONS: Pain physicians seem to lack knowledge of radiation safety and the number of physicians receiving radiation safety education is low. According to this study, education does not lead to practice. Therefore, pain physicians should receive regular radiation safety education and the education should be mandatory.

Glutamine Prevents Late-Phase Anaphylaxis via MAPK Phosphatase 1-Dependent Cytosolic Phospholipase A2 Deactivation.

BACKGROUND: Cytosolic phospholipase A2 (cPLA2) plays a key role in the development of late-phase anaphylaxis. L-Glutamine (Gln), a nonessential amino acid, has anti-inflammatory activity via inhibiting cPLA2. METHODS: We used a penicillin-induced murine model of anaphylaxis, and late-phase anaphylaxis was quantified by measuring the increase in the hematocrit (Ht) value. Various inhibitors, small interfering RNA, and knockout mice were used in inhibition experiments. Phosphorylation and protein expression of cPLA2, ERK, and MAPK phosphatase 1 (MKP-1) were detected by Western blotting. RESULTS: Leukotriene (LT) B4 was found to be another potent inducer of late-phase anaphylaxis besides the known mediator platelet-activating-factor (PAF). Gln efficiently prevented late-phase anaphylaxis when it was administered up to 3 h after challenge injection via inhibiting cPLA2. Inhibition studies indicated that p38 MAPK was the major upstream regulator of cPLA2. Gln dephosphorylated p38 and cPLA2 via up-regulating the negative regulator of p38 MAPK, i.e., MKP-1 protein. MKP-1 blockade abrogated all the effects of Gln. CONCLUSION: Of the cPLA2 metabolites, PAF and LTB4 play a key role in the development of late-phase anaphylaxis, and Gln prevents the reaction via MKP-1-dependent deactivation of cPLA2.

Spinal Cauda Equina Stimulation for Alternative Location of Spinal Cord Stimulation in Intractable Phantom Limb Pain Syndrome: A Case Report.

Phantom limb pain is a phenomenon in which patients experience pain in a part of the body that no longer exists. In several treatment modalities, spinal cord stimulation (SCS) has been introduced for the management of intractable post-amputation pain. A 46-year-old male patient complained of severe ankle and foot pain, following above-the-knee amputation surgery on the right side amputation surgery three years earlier. Despite undergoing treatment with multiple modalities for pain management involving numerous oral and intravenous medications, nerve blocks, and pulsed radiofrequency (RF) treatment, the effect duration was temporary and the decreases in the patient's pain score were not acceptable. Even the use of SCS did not provide completely satisfactory pain management. However, the trial lead positioning in the cauda equina was able to stimulate the site of the severe pain, and the patient's pain score was dramatically decreased. We report a case of successful pain management with spinal cauda equina stimulation following the failure of SCS in the treatment of intractable phantom limb pain.

Glutamine up-regulates MAPK phosphatase-1 induction via activation of Ca2+→ ERK cascade pathway.

The non-essential amino acid L-glutamine (Gln) displays potent anti-inflammatory activity by deactivating p38 mitogen activating protein kinase and cytosolic phospholipase A2 via induction of MAPK phosphatase-1 (MKP-1) in an extracellular signal-regulated kinase (ERK)-dependent way. In this study, the mechanism of Gln-mediated ERK-dependency in MKP-1 induction was investigated. Gln increased ERK phosphorylation and activity, and phosphorylations of Ras, c-Raf, and MEK, located in the upstream pathway of ERK, in response to lipopolysaccharidein vitro and in vivo. Gln-induced dose-dependent transient increases in intracellular calcium ([Ca2+]i) in MHS macrophage cells. Ionomycin increased [Ca2+]i and activation of Ras → ERK pathway, and MKP-1 induction, in the presence, but not in the absence, of LPS. The Gln-induced pathways involving Ca2+→ MKP-1 induction were abrogated by a calcium blocker. Besides Gln, other amino acids including L-phenylalanine and l-cysteine (Cys) also induced Ca2+ response, activation of Ras → ERK, and MKP-1 induction, albeit to a lesser degree. Gln and Cys were comparable in suppression against 2, 4-dinitrofluorobenzene-induced contact dermatitis. Gln-mediated, but not Cys-mediated, suppression was abolished by MKP-1 small interfering RNA. These data indicate that Gln induces MKP-1 by activating Ca2+→ ERK pathway, which plays a key role in suppression of inflammatory reactions.

The Radiation Exposure of Radiographer Related to the Location in C-arm Fluoroscopy-guided Pain Interventions.

BACKGROUND: Although a physician may be the nearest to the radiation source during C-arm fluoroscope-guided interventions, the radiographer is also near the fluoroscope. We prospectively investigated the radiation exposure of radiographers relative to their location. METHODS: The effective dose (ED) was measured with a digital dosimeter on the radiographers' left chest and the side of the table. We observed the location of the radiographers in each procedure related to the mobile support structure of the fluoroscope (Groups A, M and P). Data about age, height, weight, sex, exposure time, radiation absorbed dose (RAD), and the ED at the radiographer's chest and the side of the table was collected. RESULTS: There were 51 cases for Group A, 116 cases for Group M and 144 cases for Group P. No significant differences were noted in the demographic data such as age, height, weight, and male to female ratio, and exposure time, RAD and ED at the side of the table. Group P had the lowest ED (0.5 ± 0.8 µSv) of all the groups (Group A, 1.6 ± 2.3 µSv; Group M, 1.3 ± 1.9 µSv; P < 0.001). The ED ratio (ED on the radiographer's chest/ED at the side of the table) of Group A was the highest, and the ED radio of Group P was the lowest of all the groups (Group A, 12.2 ± 21.5%; Group M, 5.7 ± 6.5%; Group P, 2.5 ± 6.7%; P < 0.001). CONCLUSIONS: Radiographers can easily reduce their radiation exposure by changing their position. Two steps behind the mobile support structure can effectively decrease the exposure of radiographers by about 80%.

Platelet-activating factor enhances tumour metastasis via the reactive oxygen species-dependent protein kinase casein kinase 2-mediated nuclear factor-κB activation.

Platelet-activating factor (PAF) promotes tumour metastasis via activation of the transcription factor nuclear factor-κB (NF-κB). We here investigated the role of the protein kinase CK2 (formerly Casein Kinase 2 or II) in PAF-induced NF-κB activation and tumour metastasis, given that PAF has been reported to increase CK2 activity, and that CK2 plays a key role in NF-κB activation. PAF increased CK2 activity, phosphorylation and protein expression in vivo as well as in vitro. CK2 inhibitors inhibited the PAF-mediated NF-κB activation and expression of NF-κB-dependent pro-inflammatory cytokines and anti-apoptotic factors. Pre-treatment with the antioxidant N-Acetyl-L-Cysteine (NAC) resulted in a significant inhibition in PAF-induced enhancement of CK2 activity, phosphorylation and protein expression in vivo as well as in vitro. H2 O2 and known reactive oxygen species inducers, lipopolysaccharide (LPS) and tumour necrosis factor-α (TNF-α) enhanced CK2 activity, phosphorylation and protein expression, which was again inhibited by antioxidant. PAF, LPS and TNF-α induced increased CK2 activity, phosphorylationand protein expression, which were inhibited by p38 inhibitor. PAF, LPS or TNF-α increased pulmonary metastasis of B16F10, which was inhibited by antioxidants, CK2 inhibitor and p38 inhibitor. Our data suggest that (i) reactive oxygen species activate CK2 via p38, which, in turn, induces NF-κB activation, and (ii) PAF, LPS and TNF-α increase pulmonary tumour metastasis via the induction of the reactive oxygen species (ROS)/p38/CK2/NF-κB pathway.

Pneumomediastinum after arthroscopic shoulder surgery -A case report-.

An 86-year-old female with a history of right rotator cuff injury was admitted for arthroscopic shoulder surgery under general anesthesia. There were no remarkable immediate postoperative complications. However, while recovering in the general ward, she developed dyspnea with hypoxia. She was immediately treated with oxygen, and antibiotics after pneumomediastinum was confirmed on both chest x-ray and chest computed tomography. Subcutaneous emphysema on either face or neck followed by arthroscopic shoulder surgery was common, but pneumomediastinum with hypoxia is a rare but extremely dangerous complication. Thus we would like to report our case and its pathology, the diagnosis, the treatment and prevention, with literature review.

The Survey about the Degree of Damage of Radiation-Protective Shields in Operation Room.

BACKGROUND: Medical doctors who perform C-arm fluoroscopy-guided procedures are exposed to X-ray radiation. Therefore, radiation-protective shields are recommended to protect these doctors from radiation. For the past several years, these protective shields have sometimes been used without regular inspection. The aim of this study was to investigate the degree of damage to radiation-protective shields in the operating room. METHODS: This study investigated 98 radiation-protective shields in the operation rooms of Konkuk University Medical Center and Jeju National University Hospital. We examined whether these shields were damaged or not with the unaided eye and by fluoroscopy. RESULTS: There were seventy-one aprons and twenty-seven thyroid protectors in the two university hospitals. Fourteen aprons (19.7%) were damaged, whereas no thyroid protectors (0%) were. Of the twenty-six aprons, which have been used since 2005, eleven (42.3%) were damaged. Of the ten aprons, which have been used since 2008, none (0%) was damaged. Of the twenty-three aprons that have been used since 2009, two (8.7%) of them were damaged. Of the eight aprons used since 2010, one (12.3%) was damaged. Of the four aprons used since 2011, none (0%) of them were damaged. The most common site of damage to the radiation-protective shields was at the waist of the aprons (51%). CONCLUSIONS: As a result, aprons that have been used for a long period of time can have a higher risk of damage. Radiation-protective shields should be inspected regularly and exchanged for new products for the safety of medical workers.

A Randomized Controlled Trial about the Levels of Radiation Exposure Depends on the Use of Collimation C-arm Fluoroscopic-guided Medial Branch Block.

BACKGROUND: C-arm fluoroscope has been widely used to promote more effective pain management; however, unwanted radiation exposure for operators is inevitable. We prospectively investigated the differences in radiation exposure related to collimation in Medial Branch Block (MBB). METHODS: This study was a randomized controlled trial of 62 MBBs at L3, 4 and 5. After the patient was laid in the prone position on the operating table, MBB was conducted and only AP projections of the fluoroscope were used. Based on a concealed random number table, MBB was performed with (collimation group) and without (control group) collimation. The data on the patient's age, height, gender, laterality (right/left), radiation absorbed dose (RAD), exposure time, distance from the center of the field to the operator, and effective dose (ED) at the side of the table and at the operator's chest were collected. The brightness of the fluoroscopic image was evaluated with histogram in Photoshop. RESULTS: There were no significant differences in age, height, weight, male to female ratio, laterality, time, distance and brightness of fluoroscopic image. The area of the fluoroscopic image with collimation was 67% of the conventional image. The RAD (29.9 ± 13.0, P = 0.001) and the ED at the left chest of the operators (0.53 ± 0.71, P = 0.042) and beside the table (5.69 ± 4.6, P = 0.025) in collimation group were lower than that of the control group (44.6 ± 19.0, 0.97 ± 0.92, and 9.53 ± 8.16), resepectively. CONCLUSIONS: Collimation reduced radiation exposure and maintained the image quality. Therefore, the proper use of collimation will be beneficial to both patients and operators.

Progesterone increases the activity of glutamate transporter type 3 expressed in Xenopus oocytes.

Progesterone is an important sex hormone for pregnancy and also has neuroprotective and anticonvulsant effects. It is well-known that full-term parturients become more susceptible to volatile anesthetics. Glutamate transporters are important for preventing neurotoxicity and anesthetic action in the central nervous system. We investigated the effects of progesterone on the activity of glutamate transporter type 3 (EAAT3), the major neuronal EAAT. EAAT3 was expressed in Xenopus laevis oocytes by injecting its mRNA. Oocytes were incubated with diluted progesterone for 72 h. Two-electrode voltage clamping was used to measure membrane currents before, during, and after applying 30 µML-glutamate. Progesterone (1-100 nM) significantly increased EAAT3 activity in a dose-dependent manner. Our kinetic study showed that the Vmax was increased in the progesterone group compared with that in the control group (2.7 ± 0.2 vs. 3.6 ± 0.2µC for control group vs. progesterone group; n=18-23; P<0.05), however, Km was unaltered (46.7 ± 10.2µM vs. 55.9 ± 10.5µM for control group vs. progesterone group; n=18-23; P>0.05). Phorbol-12-myristate-13-acetate, a protein kinase C (PKC) activator, did not change progesterone-enhanced EAAT3 activity. Inhibitors of PKC or phosphatidylinositol 3-kinase (PI3K) abolished the progesterone-induced increases in EAAT3 activity. Our results suggest that progesterone enhances EAAT3 activity and that PKC and PI3K are involved in mediating these effects. These effects of progesterone may contribute to its anticonvulsant and anesthesia-related properties.

Chest anteroposterior diameter affects difficulty of laryngoscopy for non-morbidly obese patients.

PURPOSE: This prospective, observational study was performed to examine the hypothesis that if conventional 7-cm head elevation is applied, laryngoscopy is more difficult for patients with anteroposterior chest diameter (chest AP diameter) outside the average range (≥17.7 or ≤14.7 cm). METHODS: Chest AP diameter at the sternal notch were measured preoperatively. All patients were placed on a surgical bed with an incompressible 7-cm pillow. During laryngoscopy, the laryngeal view was graded by use of the Cormack-Lehane classification. Difficult visualization of the larynx (DVL) was defined as a grade 3 or 4 view. RESULTS: DVL was observed for 49 patients (18.2 %). Differences between measured chest AP diameter for each patient and the calculated median value were used for statistical analysis. In univariate analysis, the difference between chest AP diameter and the median value was significantly related to DVL. Logistic regression analysis confirmed that the difference between chest AP diameter and the median value was an independent predictor of DVL (odds ratio, 3.900; 95 % confidence interval, 2.371-6.415; p < 0.001). Receiver operating characteristic curve analysis showed that this test with a test threshold of 1.5 cm had reasonable diagnostic accuracy (area under the curve of 0.748). CONCLUSION: When using a standard pillow size of 7 cm, chest AP diameter above or below the average range (≥17.7 or ≤14.7 cm) was a strong predictor of DVL for apparently normal-sized patients. In such cases, modification of pillow height should be considered.

Radiation Exposure of the Hand and Chest during C-arm Fluoroscopy-Guided Procedures.

BACKGROUND: The C-arm fluoroscope is an essential tool for the intervention of pain. The aim of this study was to investigate the radiation exposure experienced by the hand and chest of pain physicians during C-arm fluoroscopy-guided procedures. METHODS: This is a prospective study about radiation exposure to physicians during transforaminal epidural steroid injection (TFESI) and medial branch block (MBB). Four pain physicians were involved in this study. Data about effective dose (ED) at each physician's right hand and left side of the chest, exposure time, radiation absorbed dose (RAD), and the distance from the center of the X-ray field to the physician during X-ray scanning were collected. RESULTS: Three hundred and fifteen cases were included for this study. Demographic data showed no significant differences among the physicians in the TFESIs and MBBs. In the TFESI group, there was a significant difference between the ED at the hand and chest in all the physicians. In physician A, B and C, the ED at the chest was more than the ED at the hand. The distance from the center of the X-ray field to physician A was more than that of the other physicians, and for the exposure time, the ED and RAD in physician A was less than that of the other physicians. In the MBB group, there was no difference in the ED at the hand and chest, except for physician D. The distance from the center of the X-ray field to physician A was more than that of the other physicians and the exposure time in physician A was less than that of the other physicians. CONCLUSIONS: In conclusion, the distance from the radiation source, position of the hand, experience and technique can correlate with the radiation dose.

Biphasic late airway hyperresponsiveness in a murine model of asthma.

BACKGROUND: Nonspecific airway hyperresponsiveness (AHR) is one of the cardinal features of bronchial asthma. Early AHR is caused by chemical mediators released from pulmonary mast cells activated in an IgE-dependent way. However, the mechanism of late AHR remains unclear. METHODS: Features of airway allergic inflammation were analyzed, including antigen-induced AHR, using a murine model of asthma. The model was suitable for examining the sequential early molecular events occurring after the initial airway exposure to antigen. RESULTS: AHR increased at 10-12 h after airway challenge, followed by the second-phase response, which was larger and broader in resistance at 18-30 h. Pretreatment of sensitized animals with anti-tumor necrosis factor (TNF) before airway challenge or induction of allergic asthma in TNF(-/-) mice resulted in abrogation of the first-phase late AHR. Intratracheal instillation of TNF induced a single peak of AHR at 10 h. IgE and IgG immune complexes induced the development of the first-phase late AHR by TNF production. Pretreatment with cytosolic phospholipase inhibitor and 5-lipoxygenase inhibitors abolished the first-phase late AHR as well as the leukotriene B(4) levels in the airway. CpG-oligodeoxynucleotide (ODN) pretreatment reduced airway levels of Th2 cytokines, eosinophil infiltration and second-phase late AHR. However, CpG-ODN did not reduce TNF levels or the magnitude of first-phase late AHR. CONCLUSION: Biphasic late AHR occurs in a murine model of asthma. First- and second-phase late AHR is caused by TNF and Th2 response, respectively.

Glutamine suppresses DNFB-induced contact dermatitis by deactivating p38 mitogen-activated protein kinase via induction of MAPK phosphatase-1.

L-glutamine (Gln) is a nonessential amino acid that is the most abundant amino acid in plasma. Gln has been reported to have an anti-inflammatory activity that involves deactivation of mitogen-activated protein kinases (MAPKs) in a MAPK phosphatase (MKP)-1-dependent manner. This study investigated the role of Gln in the inhibition of DNFB-induced allergic contact dermatitis (CD) in the ears of mice, and specifically the involvement of Gln in p38 MAPK inhibition. Topical application of Gln or the p38 inhibitor, SB202190, suppressed DNFB-induced CD. Gln application inhibited DNFB-induced p38 phosphorylation. Western blot analysis revealed that Gln application resulted in early phosphorylation and protein induction of MKP-1. MKP-1 small interfering RNA (siRNA), but not control siRNA, abrogated Gln-mediated early phosphorylation, protein induction of MKP-1, deactivation of p38, and Gln-mediated suppression of CD. The extracellular signal-regulated kinase (ERK) inhibitor, U0126, blocked Gln-induced MKP-1 phosphorylation and protein induction, as well as Gln suppression of CD. These results suggest that Gln suppresses DNFB-induced CD via deactivation of p38 MAPK through the early induction of MKP-1, the negative regulator of p38, in an ERK-dependent manner.

Glutamine suppresses airway neutrophilia by blocking cytosolic phospholipase A(2) via an induction of MAPK phosphatase-1.

Neutrophils are inflammatory cells that may contribute in a crucial way to the pathophysiology of steroid-resistant severe asthma. We previously reported that the nonessential amino acid l-glutamine (Gln) suppressed the recruitment of neutrophils into the airway in a murine model of asthma. In this study, we investigated the mechanisms by which Gln exerts beneficial effects in airway neutrophilia. We used the model we previously developed, which is suitable for examining sequential early asthmatic events, including neutrophil infiltration. Gln suppressed airway neutrophilia in a CXC chemokine-independent way. Airway neutrophilia was associated with cytosolic phospholipase A(2) (cPLA(2)) and 5-lipoxygenase (5-LO) activities. p38 MAPK, the upstream pathway of cPLA(2) and 5-LO, played a key role in inducing airway neutrophilia. Gln inhibited not only the phosphorylation of cPLA(2) and p38 MAPK but also leukotriene B(4) levels in the airways. Gln induced the early induction of MAPK phosphatase-1 (MKP-1) protein, a negative regulator of p38. MKP-1 small interfering RNA abrogated all the effects of Gln. Our results suggest that pathways involving p38/cPLA(2)/5-LO have a major role in airway neutrophilia. Gln suppresses airway neutrophilia via inhibiting p38 MAPK and its downstream pathways in an MKP-1-dependent way, which may provide a novel therapeutic strategy for pulmonary neutrophilic inflammatory diseases.

Glutamine suppresses dinitrophenol fluorobenzene-induced allergic contact dermatitis and itching: inhibition of contact dermatitis by glutamine.

BACKGROUND: Cytoplasmic phospholipase A(2) (cPLA(2)) is importantly implicated in a variety of inflammatory diseases by liberating arachidonic acid from phospholipids. The increased cPLA(2) activities as well as increased levels of cPLA(2) metabolites are associated with pathogenesis of many inflammatory skin disorders including atopic dermatitis. The non-essential amino acid l-glutamine (Gln) has been reported to have an anti-inflammatory activity. Regarding the molecular mechanism of Gln, we have recently shown that Gln effectively inhibits cPLA(2) phosphorylation and activity. OBJECTIVE: To examine whether Gln could suppress allergic contact dermatitis (CD) induced on mouse ears by dinitrophenol fluorobenzene (DNFB). METHODS: Mice were sensitized five times on their ears with a 0.15% solution of DNFB in a 3 day interval. To examine Gln effects, Gln solution (4% in saline) was applied three times a day onto both sides of DNFB-applied ears from the last day of DNFB application. The inflammatory reactions of ears were evaluated by measuring ear thickness and hematoxylin and eosin (H&E) staining. Mouse scratching behavior was objectively evaluated using a MicroAct apparatus. cPLA(2) phosphorylation and activity were analyzed using Western blotting and a cPLA(2) assay kit, respectively. RESULTS: Topical application of Gln significantly attenuated inflammatory symptoms (ear thickness, histological inflammatory skin reactions) as well as itching. Gln inhibited cPLA(2) phosphorylation and enzymatic activity. Arachidonyl trifluoromethyl ketone (AACOCF(3)) inhibited cPLA(2) activity in DNFB-challenged ears and attenuated DNFB-induced ear inflammation and itching. CONCLUSION: The results indicate that Gln suppresses DNFB-induced dermatitis and itching, at least in part, by inhibiting cPLA(2) activity.

IgG immune complex induces the recruitment of inflammatory cells into the airway and TNF-mediated late airway hyperresponsiveness via NF-κB activation in mice.

BACKGROUND: Many of the inflammatory proteins that are expressed in asthmatic airways are regulated, at least partially, by nuclear factor (NF)-κB. Blockade of NF-κB activity has resulted in attenuation of the cardinal features of asthma. Thus, delineating the mechanisms involved in NF-κB activation in asthma might provide an interesting approach to improving the management of asthma. However, despite its importance, the mechanism for NF-κB activation in asthma has not yet been determined. OBJECTIVE: To examine the role of IgE and IgG antibodies (Abs) in the activation of NF-κB in mouse lungs. METHODS: To examine the effect of IgE, mice underwent intratracheal (i.t.) instillation of an IgE immune complex (IgE-IC) (anti-2,4-dinitrophenyl hapten (DNP) IgE + DNP-BSA or DNP-OVA) and anaphylactogenic anti-IgE (LO-ME-2). For IgG, mice underwent i.t. instillation with a complex of anti-chicken gamma globulin (CGG) IgG1 mAb + CGG. NF-κB activation was determined by gel shift assay. Small interfering RNA was used for blockade of p50 expression. The effect of tumor necrosis factor (TNF) blockade was determined using anti-TNF Ab. A previously established murine model of asthma was used to assess airway hyperresponsiveness (AHR). RESULTS: A single i.t. instillation of either IgE-IC or LO-ME-2 failed to induce activation of NF-κB in the lungs. In contrast, single i.t. instillation of IgG-IC was capable of inducing NF-κB activation, as well as NF-κB-dependent proinflammatory molecules, such as TNF and CXC chemokines. Pretreatment of p50 small interfering RNA decreased bronchoalveolar lavage fluid levels of TNF and macrophage inflammatory protein-2 induced by IgG-IC instillation. Single i.t. instillation of IgG-IC caused the recruitment of neutrophils and macrophages into the airway and TNF-mediated late AHR, but failed to induce Th2 cell-mediated asthmatic phenotypes. CONCLUSION: IgG, but not IgE, is the major Ab that induces not only NF-κB activation and NF-κB-dependent proinflammatory molecules in the lungs but also subsequent recruitment of inflammatory cells into the airway and TNF-mediated late AHR.