The Inhibition Effect and Mechanism of Staurosporine Isolated from Streptomyces sp. SNC087 Strain on Nasal Polyp.

This study aims to explore the potential inhibition effects of staurosporine isolated from a Streptomyces sp. SNC087 strain obtained from seawater on nasal polyps. Staurosporine possesses antimicrobial and antihypertensive activities. This research focuses on investigating the effects of staurosporine on suppressing the growth and development of nasal polyps and elucidating the underlying mechanisms involved. The experimental design includes in vitro and ex vivo evaluations to assess the inhibition activity and therapeutic potential of staurosporine against nasal polyps. Nasal polyp-derived fibroblasts (NPDFs) were stimulated with TGF-ß1 in the presence of staurosporine. The levels of α-smooth muscle actin (α-SMA), collagen type-I (Col-1), fibronectin, and phosphorylated (p)-Smad 2 were investigated using Western blotting. VEGF expression levels were analyzed in nasal polyp organ cultures treated with staurosporine. TGF-ß1 stimulated the production of Col-1, fibronectin, and α-SMA and was attenuated by staurosporine pretreatment. Furthermore, these inhibitory effects were mediated by modulation of the signaling pathway of Smad 2 in TGF-ß1-induced NPDFs. Staurosporine also inhibits the production of VEGF in ex vivo NP tissues. The findings from this study will contribute to a better understanding of staurosporine's role in nasal polyp management and provide insights into its mechanisms of action.

A Case of Cavernous Hemangioma on the Lateral Wall of the Inferior Nasal Meatus.

Hemangiomas, which originate in the sinonasal area, are not common among the various types of tumors from the head and neck region. Mechanisms for the formation of the tumor are yet to be discovered, and a few factors such as trauma, infection, oncogene, and some hormones are considered to take a role in the occurrence and growth of the tumor. Hemangiomas are classified for their histologic features as cavernous, capillary, and mixed types. There are a few reported cases of cavernous hemangiomas of the maxillary sinus, ethmoid sinus, middle and inferior nasal turbinate, and nasal septum. However, a case of cavernous hemangioma from the inferior nasal meatus, on the lateral wall to be precise, has never been reported. The authors are the first to report a case of a 69-year-old female patient who had cavernous hemangioma which was originated from the lateral wall of the inferior nasal meatus and successfully managed.

A Patient of Venous Hemangioma of the Inferior Turbinate.

Sinonasal hemangiomas are relatively rare among the hemangiomas that occur from the head and neck parts. According to their histopathologic findings, they are classified as capillary, cavernous, or venous type. Some cases of capillary or cavernous hemangioma that occur from the inferior turbinate have been reported. However, there was no reported case of venous hemangioma arising from the inferior turbinate. We present a case of 67-year-old male who has venous hemangioma of the left inferior turbinate whose initial symptoms were watery rhinorrhea and postnasal drip. With this study, although uncommon, venous hemangioma should be considered as a differential diagnosis in patient with mass lesion of the inferior turbinate.

Antifibrosis Efficacy of Apo-9-Fucoxanthinone-Contained Sargassum horneri Ethanol Extract on Nasal Polyp: An In Vitro and Ex Vivo Organ Culture Assay.

Sargassum horneri is a seaweed species with diverse bioactivities. However, its antifibrotic effects during nasal polyp (NP) formation are not clearly understood. Therefore, we investigated the inhibitory effect of S. horneri on fibrosis progression in NP-derived fibroblasts (NPDFs) and NP tissues ex vivo. NPDFs were stimulated with TGF-ß1 in the presence or absence of S. horneri ethanol extract (SHE). The extracellular matrix (ECM) protein production levels, myofibroblast differentiation (α-smooth muscle actin, α-SMA), and phosphorylation of Smad 2/3 and -ERK in TGF-ß1-stimulated NPDFs were investigated using western blotting. Further, the contractile activity of SHE was assessed by performing a collagen gel contraction assay. The expression levels of collagen-1, fibronectin, and α-SMA were investigated in NP organ cultures treated with SHE. TGF-ß1 stimulated ECM protein expression, myofibroblast differentiation, and collagen contractile activity while these were attenuated by pretreatment with SHE. We also found antifibrotic effect of SHE on ex vivo NP tissues. The antifibrotic effects of SHE were modulated through the attenuation of Smad 2/3 and ERK signaling pathways in TGF-ß1-stimulated NPDFs. In conclusion, SHE inhibited ECM protein accumulation and myofibroblast differentiation during NP remodeling. Thus, SHE may be helpful as a treatment for NP recurrence after endoscopic sinus surgery.

Extranasopharyngeal Angiofibroma of the Natural Ostium of Maxillary Sinus.

ABSTRACT: Extranasopharyngeal angiofibroma which occurs in all head and neck regions is extremely rare. Unlike most angiofibromas which show nasal congestion and recurrent epistaxis as their symptoms, extranasopharyngeal angiofibromas (ENAF) may lead to various symptoms depending on their location. Nasal septum is the most frequent site of origin of ENAF. No study of ENAF originating in natural ostium of maxillary sinus has been reported. We present a case of 27-year-old male who has extranasophar- yngeal angiofibroma arising from the natural ostium of maxillary sinus in an adult patient whose symptom was right sided nasal obstruction. With this study, although uncommon, angiofibroma should be considered as a differential diagnosis in patient with mass lesion in the middle nasal meatus.

Endoscopic Intranasal Marsupialization of the Isolated Mucocele in the Inferior Orbit.

ABSTRACT: Isolated intraorbital mucocele without anatomical communication between the sinus and orbital cavity, and all orbital walls are intact is rare. It may lead to many orbital symptoms including proptosis, diplopia, orbital pain. Traditionally, many cases of typical paranasal sinus mucocele are successfully treated with endoscopic marsupialization. Most of the isolated intraorbital mucoceles were treated with complete removal of the mucocele via an external approach. However, there are many disadvantages of the external approach, and a case of isolated intraorbital mucocele in medial orbit treated by endoscopic intranasal marsupialization was reported. Here, the authors report a case of isolated orbital mucocele in inferior orbit treated by endoscopic intranasal marsupialization.

Fucoxanthin Inhibits Myofibroblast Differentiation and Extracellular Matrix Production in Nasal Polyp-Derived Fibroblasts via Modulation of Smad-Dependent and Smad-Independent Signaling Pathways.

Nasal polyps (NPs) are a multifactorial disorder associated with a chronic inflammatory state of the nasal mucosa. Fucoxanthin (Fx) is a characteristic orange carotenoid obtained from brown algae and has diverse immunological properties. The present study investigated whether Fx inhibits fibrosis-related effects in nasal polyp-derived fibroblasts (NPDFs) and elucidated the molecular signaling pathways involved. The production of collagen type I (Col-1) was investigated in NP tissue via immunohistochemistry and western blot analysis. NPDFs were treated with transforming growth factor (TGF)-ß1 (1 ng/mL) in the presence or absence of Fx (5⁻30 µM). The levels of α-smooth muscle actin (α-SMA), Col-1, and phosphorylated (p)-Smad 2/3, signal protein-1 (SP-1), MAPKs (mitogen-activated protein kinases), and Akt were measured by western blot analysis. The expression of Col-1 was detected in NP tissues. TGF-ß1 stimulated the production of α-SMA and Col-1, and stimulated the contraction of collagen gel. However, pretreatment with Fx attenuated these effects. Furthermore, these inhibitory effects were mediated through modulation of both Smad 2/3 and Akt/SP-1 signaling pathways in TGF-ß1-induced NPDFs. The results from the present study suggest that Fx may be a novel anti-fibrotic agent for the treatment of NP formation.

Effect of phlorotannins on myofibroblast differentiation and ECM protein expression in transforming growth factor ß1­induced nasal polyp­derived fibroblasts.

Phlorotannins (PTNs), a group of phenolic compounds from seaweeds, have diverse bioactivities. However, there has been no report on their antifibrotic effects during nasal polyp (NP) formation. In the present study, the effect of PTNs on transforming growth factor (TGF)­ß1­induced profibrotic responses in nasal polyp­derived fibroblasts (NPDFs) were determined and the relevant signaling pathways were investigated. The expression levels of collagen type­1 (Col­1) and fibronectin in NP tissues were measured by western blot analysis and immunohistochemistry. The NPDFs were treated with TGF­ß1 (1 ng/ml) in the presence or absence of PTNs (5­30 µg/ml). The expression levels of α­smooth muscle actin (α­SMA), Col­1, fibronectin, and phosphorylated­small mothers against decapentaplegic (Smad)2/3 in NPDFs were measured by western blot analysis. The contractile activity of the NPDFs was determined by a collagen gel contraction assay. Col­1 and fibronectin proteins were found to be expressed in NP tissues. PTNs had no significant cytotoxic effect on TGF­ß1­induced NPDFs. TGF­ß1 induced the expression α­SMA, Col­1 and fibronectin, and stimulated fibroblast­mediated contraction of collagen gel. However, pre­treatment with PTNs inhibited the expression of these proteins. The inhibitory effects were mediated through the suppression of Smad2/3 signaling pathways in TGF­ß1­induced NPDFs. These resulted suggested that PTNs may be important in inhibiting myofibroblast differentiation and extracellular matrix protein accumulation in NP formation through the Smad2/3 signaling pathway.

Anti-inhibitory potential of an ethanolic extract of Distromium decumbens on pro-inflammatory cytokine production in Pseudomonas aeruginosa lipopolysaccharide-stimulated nasal polyp-derived fibroblasts.

Marine algae are rich sources of biologically active compounds that may present useful leads in the development of pharmaceuticals, nutraceuticals, and functional foods. The main aim of this study was to identify the possible anti-inflammatory effects of Distromium decumbens in nasal polyp-derived fibroblasts (NPDFs) and its associated mechanism of action. NPDFs were stimulated by Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) and treated with an ethanolic extract of Distromium decumbens (DDE). The production of interleukin-6 (IL-6) and IL-8 in the supernatant, the phosphorylation of mitogen-activated protein kinase (MAPK) molecules [extracellular signal-related kinase 1/2 (ERK1/2), c-Jun N-terminal kinase and p38 MAPK] and Akt, and the activation of nuclear factor-κB (NF-κB) were assayed in the PA-LPS-stimulated NPDFs untreated or treated with DDE. The expression levels of IL-6 and IL-8 in PA-LPS-exposed NPDFs were detected using enzyme-linked immunosorbent assays. The mechanisms by which DDE regulates cellular signaling cascades were investigated using electrophoretic mobility shift assays and western blot analysis. Functional validation was performed by measuring the inhibitory effects of DDE on neutrophil migration in vitro. DDE reduced the expression of IL-6 and IL-8 stimulated by PA-LPS in NPDFs. The activation of ERK1/2, Akt and NF-κB by PA-LPS was inhibited by DDE. Inhibitors of ERK1/2, Akt and NF-κB inhibited the expression of IL-6 and IL-8. In addition, DDE significantly attenuated PA-LPS-induced migration of differentiated HL-60 cells. The present findings suggest that DDE potently inhibits inflammation through the ERK1/2, Akt and NF-κB signaling pathways in NPDFs.

Methotrexate Induces Apoptosis in Organ-Cultured Nasal Polyps Via the Fas Pathway.

OBJECTIVE: Methotrexate (MTX) is very effective when used to treat chronic inflammatory diseases, and also induces apoptosis in nasal polyps (NPs). Increasing evidence suggests that Fas-Fas ligand (FasL) interactions activate multiple pathways involved in the regulation of immune and inflammatory cell functions. The aim of the present study was to identify pathways activated by Fas signaling when NPs were treated with MTX. METHODS: Nasal polyps tissues were cultured using an air-liquid interface organ culture method. Cultures were maintained in the absence or presence of MTX (10 or 100 µM) for 24 hours. The authors used the reverse transcription-polymerase chain reaction method and Western blotting to identify pathways activated by Fas when NPs were treated with MTX. RESULTS: The Fas mRNA expression ratio was unchanged upon MTX treatment, but the FasL mRNA expression ratio was significantly higher in MTX-treated than nontreated polyps. In addition, the expression levels of the Fas and FasL proteins were significantly higher in polyps treated with both 10 and 100 µM MTX compared with nontreated polyps. CONCLUSIONS: Methotrexate induces apoptosis in NPs via the Fas pathway. Future studies should explore the topical use of MTX for NP control. Methotrexate may be a useful alternative steroid-sparing agent for the treatment of NPs.

Expression of ADAM17 and ADAM10 in nasal polyps.

BACKGROUND: The "a disintegrin and metalloproteases" (ADAMs) are a multifunctional gene family that contribute to the homeostasis of the extracellular matrix, transduction of specific intracellular signals, organogenesis, inflammation, tissue remodeling, adhesion, and cell migration. ADAM17 is the best-characterized of the "sheddases," and its putative substrates are widespread, including various inflammatory modulators. ADAM10 is the most similar to ADAM17 in terms of protein sequence and the structural properties of their catalytic domains. The objective of this work was to assess the roles of ADAM17 and ADAM10 in nasal polyps (NPs) by measuring their expression. METHODS: The expression of ADAM10 and 17 was investigated in NPs at endonasal sinus surgery (n = 15) and compared with that in inferior turbinate mucosa samples obtained from nonallergic hypertrophic rhinitis patients (n = 15). Tissue samples were analyzed by real-time polymerase chain reaction (PCR), Western blotting, and immunohistochemical staining. RESULTS: The ADAM17 messenger RNA (mRNA) and protein levels were significantly higher in the inferior turbinate than in NPs (p < 0.05). The ADAM10 mRNA and protein levels did not differ significantly between NPs and inferior turbinates (p > 0.05). ADAM10 and ADAM17 were expressed primarily in inflammatory cells, submucosal glandular cells, and lining epithelial cells. CONCLUSION: ADAM17 may contribute to the development of NPs in contrast to ADAM10, based on their expression patterns. It may be important to discover the role of ADAM17 in the development of NP and helpful to examine the specific mechanism of the development of NPs.

Expression profile of ADAM10 and ADAM17 in allergic rhinitis.

BACKGROUND: A disintegrin and metalloprotease (ADAM) is a multifunctional gene family that contributes to the homeostasis of the extracellular matrix, transduction of specific intracellular signals, organogenesis, inflammation, tissue remodeling, adhesion, and cell migration. ADAM17 is the best characterized sheddase, with widespread putative substrates, including various inflammatory modulators. ADAM10 is the most similar ADAM to ADAM17 in terms of both protein sequence and the structural properties of their catalytic domains. The objective of this work was to assess the expression of ADAM10 and ADAM17 in allergic rhinitis to gain insight into their respective roles. METHODS: The expression of ADAM10 and ADAM17 was investigated in the nasal mucosa under allergic and nonallergic conditions. Tissue samples were evaluated by reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting, and data were analyzed semiquantitatively with densitometry. RESULTS: The ADAM17 messenger RNA (mRNA) level was significantly (p < 0.001) lower in the allergic nasal mucosa than in the nonallergic nasal mucosa, whereas the ADAM10 mRNA level was significantly (p < 0.001) lower in the nonallergic nasal mucosa. The ADAM17 protein levels were also significantly (p < 0.001) lower in the allergic nasal mucosa, whereas the ADAM10 protein levels were lower in the nonallergic nasal mucosa (p = 0.002). CONCLUSION: Decreased expression of ADAM17 and increased expression of ADAM10 may contribute to the development of allergic rhinitis through unknown pathways. We suggest that understanding the expression profile of ADAM17 and ADAM10 might help to elucidate the mechanism of allergic rhinitis.

Dexamethasone Induces Apoptosis of Nasal Polyp-Derived Tissue Cultures Through JNK and p38 MAPK Activation.

OBJECTIVES: Glucocorticoids, such as dexamethasone (DEX), increase apoptosis in a variety of white cells in nasal polyps and apoptosis is an important factor in the resolution of inflammation. However, the mechanism of glucocorticoids induced apoptosis in nasal polyp remains unclear. In this study the authors evaluated which pathways were engaged in apoptosis induced by DEX in an ex vivo model of nasal polyps. METHODS: Nasal polyp tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of DEX (10 or 100 µM) for 24 hours. To investigate the involvement of the apoptotic signaling pathways in nasal polyp, such as caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 mitogen-activated protein kinase (MAPK)/JNK pathway, the authors performed reverse transcription-polymerase chain reaction and Western blotting. RESULTS: The expression ratios of FasL, activated form of caspase-8, caspase-9, and caspase-3 were significantly higher in DEX-treated polyps (P<0.01). In the Bcl-2 family expression, the anti-apoptotic molecules, Bcl-2 and Bcl-XL decreased, but pro-apoptotic molecules, Bax increased, and Bid and Bad were activated. In the conventional MAPKs, JNK, and the phospho-p38 MAPK were significantly higher, but phospho-extracellular signal-regulated kinase (ERK)1/2 was significantly lower in DEX-treated polyps (P<0.01). CONCLUSION: DEX induces apoptosis of nasal polyp via caspase cascades, Fas-FasL signaling pathway, mitochondrial pathway and p38 MAPK/JNK pathway.

Nasal polyp chitinolytic activity associated with smoking or allergy.

BACKGROUND: Cells of the innate immune system that are implicated in allergy and immunity bind to chitin during tissue infiltration in a process negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) exert chitinolytic activity. The levels of activities of these enzymes in nasal polyps (NPs) of subjects who smoke or who suffer from allergies are unknown. In the present work, we measured the activities of AMCase and ChT in NPs of smokers and allergic subjects. METHODS: We report a prospective cohort study in a tertiary care facility. AMCase and ChT activities of NPs were measured in buffers of several pH values using the fluorogenic substrate 4-methylumbelliferyl-ß-d-N,N',N″-triacetyl-chitotriose. RESULTS: The activities of AMCase and ChT in NPs did not differ significantly among smokers, nonsmokers, and ex-smokers. AMCase and ChT activities were significantly higher in NPs of allergic subjects than in NPs of those who did not suffer from allergy. CONCLUSION: Increased levels of chitinolytic activities in NPs were associated with the allergic rhinitis. We suggest that control of such rhinitis may help to prevent the development and growth of NPs.

Methotrexate induces apoptosis in nasal polyps via caspase cascades and both mitochondria-mediated and p38 mitogen-activated protein kinases/Jun N-terminal kinase pathways.

BACKGROUND: Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases that induces apoptosis in nasal polyps (NPs). However, the precise apoptotic pathway in NPs remains unclear. The aim of this study was to identify the apoptotic signaling pathways activated by MTX in NPs. METHODS: NP tissues were organ cultured using an air-liquid interface method. Cultures were maintained in the presence or absence of MTX (10 or 100 µM) for 24 hours. To investigate apoptotic signaling in NPs, we performed reverse transcription-polymerase chain reaction and Western blotting. RESULTS: MTX-treated NPs contained significantly increased amounts of the active forms of caspase 8, caspase 9, and caspase 3 and displayed increased cleavage of poly(ADP-ribose) polymerase. Expression of the proapoptotic molecules Bax and Bad at the mRNA and protein levels and of the activated molecules p-Bad and tBid was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the antiapoptotic molecule Bcl-2 at the mRNA and protein levels was significantly lower in MTX-treated NPs than in nontreated NPs. Expression of the phosphorylated forms of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) was significantly higher in MTX-treated NPs than in nontreated NPs. In contrast, expression of the phosphorylated form of Akt was significantly lower in MTX-treated NPs than in nontreated NPs. CONCLUSION: MTX induces apoptosis in NPs via caspase cascades and both mitochondria-mediated and p38 MAPK/JNK pathways. We suggest that MTX can be used to treat NPs.

Effects of dexamethasone or methotrexate on chitinolytic activity in nasal polyps.

BACKGROUND: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and immunity. This process can be negatively regulated by vertebrate chitinases. Chitinolytic activity is significantly increased in nasal polyps (NPs) compared with that in normal turbinate mucosa. Dexamethasone (DEX) or methotrexate (MTX) is an effective treatment for chronic inflammatory diseases. The aim of this study was to investigate the effects of DEX or MTX on chitinolytic activity in organ-cultured NPs. METHODS: NP tissues were cultured using an air-liquid interface culture model. Cultures were maintained for 24 hours in the absence or presence of DEX (10 or 100 micromolar) or MTX (10 or 100 micromolar). Acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) activities in tissue samples were measured at a range of pH values by using the fluorogenic substrate 4-methylumbelliferyl-beta-(D)-N,N',N″-triacetyl-chitotriose. RESULTS: AMCase and ChT chitinolytic activities were significantly lower in NPs treated with 100 micromolar DEX or 100 micromolar MTX than that in fresh or untreated NPs. AMCase chitinolytic activity tended to be lower in DEX-treated polyps than in MTX-treated polyps, although the difference was not statistically significant. CONCLUSION: DEX or MTX reduced chitinolytic activity in NPs. We suggest that DEX or MTX may inhibit the growth of NPs via local regulation of NP chitinolytic activity.

Effects of methotrexate on vascular endothelial growth factor, angiopoietin 1, and angiopoietin 2 in nasal polyps.

BACKGROUND: Methotrexate (MTX) is a very effective treatment for chronic inflammatory diseases, which are often associated with increased angiogenesis. Angiogenesis is dependent on a perfectly coordinated balance between endogenous-positive and -negative regulatory factors, including vascular endothelial growth factor (VEGF) and the angiopoietins (Ang). The aim of this study was to investigate the effects of MTX on levels of VEGF, Ang-1, and Ang-2 in organ-cultured nasal polyps (NPs). METHODS: To determine the effects of MTX, NP tissues were cultured using an air-liquid interface method. Cultures were maintained in the absence or presence of MTX (10 or 100 micromoles) for 24 hours. Hematoxylin and eosin, and TUNEL (terminal deoxynucleotidyl transferase [Tdt]-mediated dUTP-biotin nick-end labeling) staining were performed to observe apoptosis. Enzyme-linked immunosorbent assay was used to quantify tissue concentrations of VEGF, Ang-1, and Ang-2. RESULTS: MTX treatment resulted in marked alterations in inflammatory cells, especially eosinophils. In contrast, the mucosal epithelium, microvessels including arterioles, veins and capillaries, and fibroblasts maintained their structure. TUNEL(+) cells (apoptotic cells) were seen in the MTX-treated specimens. The more induction of TUNEL(+) cells was observed 100-micromolar MTX-treated specimens. VEGF and Ang-1 levels were significantly lower, and Ang-2 levels were significantly higher in NPs treated with 100-micromolar MTX than in nontreated NPs (p < 0.01). CONCLUSION: MTX may inhibit the growth of NPs via local regulation of VEGF, Ang-1, and Ang-2 protein levels. We suggest that MTX can be used to treat NPs.

Expression of galectin-9 by IFN-γ stimulated human nasal polyp fibroblasts through MAPK, PI3K, and JAK/STAT signaling pathways.

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) may play important roles in the selective recruitment of eosinophils in nasal polyp tissues through the production of galectin-9. These findings suggest that galectin-9 expression is associated with eosinophil infiltration in polyps of patients with nasal polyposis.

Chitinolytic activity in nasal polyps.

BACKGROUND: Chitin is a recognition element for tissue infiltration by innate cells implicated in allergy and immunity. This process can be negatively regulated by vertebrate chitinases. Both acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) have chitinolytic activity. This study aimed to determine the activities of AMCase and ChT in nasal polyps (NPs), as well as their in situ localization in NP tissue. METHODS: AMCase and ChT activities in NPs were compared with those in inferior turbinate tissue samples. Tissue samples were measured for AMCase and ChT activities at a range of pHs using the fluorogenic substrate 4-methylumbelliferyl-beta-d-N,N',N''-triacetyl-chitotriose. Double immunofluorescent staining for the localization of both AMCase and ChT was performed using NP cryosections. RESULTS: Both AMCase and ChT displayed markedly increased chitinolytic activity in all NPs, compared with inferior turbinate tissues. Double immunofluorescent staining revealed that CD68 highlighted monocytes in the submucosa of NP and these cells disclosed coexpression of AMCase and ChT. CD31 detected capillary endothelial cells, but did not express any AMCase and ChT. CONCLUSION: The increased chitinolytic activities of AMCase and ChT in NPs may be important in NP pathogenesis, suggesting that inhibition of chitinolytic activity may be a novel therapeutic strategy for the treatment of NPs.

Expression of chitinases in hypertrophied adenoids of children.

OBJECTIVES/HYPOTHESIS: Chronic rhinosinusitis (CRS), otitis media with effusion (OME), and allergic rhinitis (AR) are common conditions that have been associated with hypertrophied adenoids in children, and adenoidectomy is clinically recommended. The investigators assayed the expression level and site of acidic mammalian chitinase (AMCase) and chitotriosidase (ChT) in hypertrophied adenoids of children to determine the expression levels of 2 chitinases in relation to CRS, OME, and AR. STUDY DESIGN: A prospective cohort study. SETTING: A tertiary care facility. METHODS: Hypertrophied adenoids from 41 children were harvested during adenoidectomy. Medical records were reviewed and the subjects were grouped according to the presence of CRS, OME, and AR. Messenger RNA (mRNA) and protein expression of AMCase and ChT in adenoid tissues was assessed by reverse transcription polymerase chain reaction and Western blotting. Immunohistochemical staining revealed the sites of AMCase and ChT expression. RESULTS: mRNA and protein of AMCase and ChT were present in adenoids of all subjects. CRS was a significant variable in AMCase mRNA and protein expression. CRS, OME, and AR were significant variables in ChT mRNA and protein expression. Both AMCase and ChT were expressed in histiocytes and vascular endothelial cells of adenoid tissues. CONCLUSIONS: The findings suggest that chitin-containing pathogens or dysregulated immune responses to them in the hypertrophied adenoids of children could be factors contributing to CRS, OME, and AR via AMCase or ChT overexpression.