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Infection is one of the main causes of death in clinical patients, and multi-drug resistance leads to ineffective treatment with conventional antibiotics. Therefore, it is imperative to develop new anti-infective drugs. Antimicrobial peptides cathelicidins are cationic host defense peptides found in many organisms. It has been demonstrated by in vivo and in vitro studies that antimicrobial peptides cathelicidins not only show broad-spectrum antibacterial activity and high sensitivity to drug-resistant bacteria, but also have a good guiding effect on the immune response. This paper summarizes the reports of antimicrobial peptides cathelicidins in recent years, highlighting their research achievements in antibiosis, anti-inflammatory, chemotaxis regulation and phagocytosis, providing new ideas for the treatment of infection-related diseases.
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Infection is one of the main causes of death in clinical patients, and multi-drug resistance leads to ineffective treatment with conventional antibiotics. Therefore, it is imperative to develop new anti-infective drugs. Antimicrobial peptides cathelicidins are cationic host defense peptides found in many organisms. It has been demonstrated by in vivo and in vitro studies that antimicrobial peptides cathelicidins not only show broad-spectrum antibacterial activity and high sensitivity to drug-resistant bacteria, but also have a good guiding effect on the immune response. This paper summarizes the reports of antimicrobial peptides cathelicidins in recent years, highlighting their research achievements in antibiosis, anti-inflammatory, chemotaxis regulation and phagocytosis, providing new ideas for the treatment of infection-related diseases.
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ABSTRACT Purpose: To investigate human beta-defensins (HBDs) and cathelicidin LL-37 (LL-37) expressions in patients with pterygium. Methods: In this retrospective consecutive case series, 26 pterygium specimens and 15 normal conjunctival specimens of 15 control subjects were in vestigated. Expressions of HBD-1, HBD-2, HBD-3, and LL-37 were assessed using immuno histochemical staining. A brown color in the cytoplasm and/or nuclei of epithelial cells indicated positive staining for HBDs and LL-37. For each antibody, the intensity of the reaction (negative [-], weak [1+], moderate [2+], or strong [3+]) was determined to describe the immunoreactions. Results: The median age was 52 years in both groups. There were no significant differences in age and sex between the groups (p=0.583, p=0.355, respectively). Of the 26 pterygium specimens, 15 (57.7%) (14 weak, 1 moderate staining) showed HBD-2 expression, which was not observed in any of the control specimens. One (3.8%) pterygium and one (6.7%) control specimen demonstrated weak staining for HBD-3. HBD-2 expression was significantly higher in the pterygium specimens than in the controls (p=0.002). None of the tissue specimens had positive staining for HBD-1 or LL-37 in either group (both; p=1.00). Conclusions: HBD-2 expression was higher in pterygium specimens than in the controls. HBD-2 expression that might be stimulated by inflammatory cytokines may be related to inflammation and fibrovascular proliferation and may play a role in pterygium pathogenesis.
RESUMO Objetivo: Investigar as expressões beta defensinas humanas (HBD) e catelicidina em pacientes com pterígio. Métodos: Nesta série de casos retrospectivos consecutivos, 26 espécimes de pterígio e 15 espécimes conjuntivais normais de 15 indivíduos controle foram investigados. As expressões de HBD-1, HBD-2, HBD-3 e catelicidina (LL-37) foram avaliadas por coloração imuno-histoquímica. Uma cor castanha no citoplasma ou nos núcleos de células epiteliais foi definida como coloração positiva para HBDs e LL-37. Para cada anticorpo foi determinada a intensidade da reação (negativo [-], fraco [1+], moderado [2+] ou forte [3+]) para descrever as imunoreações. Resultados: A idade média foi de 52 anos em ambos os grupos. Não houve diferença significativa entre os grupos em termos de idade e sexo (p=0,583, p=0,355, respectivamente). Das 26 amostras de pterígio, 15 (57,7%) (14 fracas e 1 moderada) demonstraram a expressão de HBD-2 enquanto não foi encontrada em nenhum dos espécimes de controlo. Um dos pterígios (3,8%) e um dos espécimes de controlo (6,7%) demonstraram fraca coloração para HBD-3. A expressão de HBD-2 foi significati vamente maior nos espécimes de pterígio do que nos controles (p=0,002). Nenhum dos espécimes de tecido apresentou coloração positiva para HBD-1 ou LL-37 em ambos os grupos (ambos p=1,00). Conclusão: Encontramos aumento da expressão de HBD-2 em espécimes de pte rígio em relação aos controles. A expressão de HBD-2 que pode ser estimulada por citocinas inflamatórias pode estar relacionada com inflamação e proliferação fibrovascular e pode desempenhar um papel na patogênese do pterígio.
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Humans , Male , Female , Adult , Middle Aged , Aged , Pterygium/metabolism , Antimicrobial Cationic Peptides/analysis , beta-Defensins/analysis , Reference Values , Biopsy , Immunohistochemistry , Case-Control Studies , Retrospective Studies , Statistics, Nonparametric , Conjunctiva/chemistryABSTRACT
Objective To evaluate effects of artesunate on rosacea-like inflammation in mouse models.Methods Twenty-five male BALB/c mice aged 7 weeks were injected subcutaneously with 40 μ1 antibacterial peptide LL-37 into the back once every 12 hours for 4 sessions to establish mouse models with rosacea-like inflammation.These 25 mice were randomly and equally divided into 5 groups:after each injection of LL-37,model group were gavaged with sodium chloride physiological solution,treatment groups gavaged with 25,50 and 100 mg/kg artesunate solution separately,and positive control group gavaged with 30 mg/kg doxycycline hydrochloride solution.Another 5 healthy mice injected subcutaneously with pure water into the back for 4 sessions served as blank control group.Forty-eight hours after the initial injection of LL-37,changes in skin lesions and the intensity of erythema were assessed.Skin tissues at the dorsal injection site were resected and subjected to HE staining,the tissue structure was observed and the number of inflammatory cells was counted.Enzyme-linked immunosorbent assay (ELISA) was performed to estimate the activity of myeloperoxidase (MPO) in skin lesions.Results The model group showed obvious inflammatory reactions,and significantly increased erythema score (3.20 ± 0.84),inflammatory cell count (517.27 ± 99.43) and MPO activity (0.57 ± 0.08) compared with the blank control group (all P ＜ 0.01).The positive control group showed significantly decreased erythema score (1.60 ± 0.89),inflammatory cell count (270.93 ± 124.63) and MPO activity (0.40 ± 0.05) compared with the model group (P ＜ 0.05,0.01,0.01,respectively).Moreover,the erythema score,inflammatory cell counts and MPO activity were all significantly lower in 50-(1.80 ± 0.84,286.00 ± 33.72,0.43 ± 0.05,respectively) and 100-mg/kg artesunate groups (1.40 ± 0.55,258.00 ± 36.44,0.40 ± 0.06,respectively) than in the model group (P ＜ 0.05 or 0.01).However,there were no significant differences in the erythema score,inflammatory cell count and MPO activity between 50-or 100-mg/kg artesunate group and the positive control group (P ＞ 0.05).Conclusion Artesunate can inhibit rosacea-like inflammatory reactions in mouse models,especially the middle-and high-dose artesunate.
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Cathelicidins play critical roles in mammalian innate immune defense against invasive bacterial infection. In addition to their broad-spectrum bactericidal effect, cathelicidins are interesting peptide-based drug templates because they have multiple functions including anti-inflammatory, wound healing, and angiogenesis promotion. This article summarizes the aim and method of cathelicidin molecular designs. Residue mutation, fragment assembly, chemical modification, and construction of conjugates and dimers are usually used to increase the biological activities. Addition or deletion of certain residues, disruption of leucine zipper and phenylalanine zipper are used to reduce the hemolysis and cytotoxicity. By substituting L-amino acids with D-amino acids, circular constructions and immobilization, cathelicidins' in vitro and in vivo stability could be greatly enhanced, especially their proteinase resistance.
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Objective The antimicrobial peptide LL-37 ( LL-37) is the mature form of Human Cationic Antimicrobial Pep-tide of 18kD (hCAP18) and play a certain regulation role in the pathogenesis of asthma .However, the mechanism is unclear.The aim of this study was to investigate the role of inflammatory release from human eosinophils induced by the antimicrobial peptide LL -37 in the pathogenesis of asthma and the underlying mechanisms . Methods Sixteen mild or medium allergic asthma patients from January 2015 to January 2016 in Panzhihua college affiliated hospital were enrolled .Another 16 healthy volunteers were enrolled as control .Pri-mary eosinophils were isolated from peripheral blood .The cells were divided into two groups:asthma group and healthy control group . Cells were divided into blank , PAF, LL37, single cytokine ( IL-5, GM-CSF) and cytokines combined with LL-37 group based on in-tervention (cell treating factors) difference;Cells were divided into PTx, WRW4, suramin, and LL-37 combined with inhibitors group based on inhibitors difference;Cells were grouped into LTD 4 and LTB4 treatment based on leukotrienen difference;ELISA was applied to analyze cysteinyl leukotrienes ( cys-LTs) level in various treatment groups;Western blot was used to detect change of cPLA 2, p-cP-LA2, ERK1/2, p-ERK1/2 in the cells from the control group after PTx and WRW 4 treatment and the level of hCAP 18 after leukot-riene treatment. Results Compared with the control 15 μg/mL LL-37 sub group, the expression of Cys-LTs was increased in the control 30μg/mL LL-37 sub group 15 and 30 minutes after the LL-37 treatment [(54.02±7.15) pg/105 vs (37.86±6.33) pg/105, (53.30±6.99) pg/105 vs (36.27±6.46) pg/105, P<0.05].Compared with the control IL-5 sub group (26.18±4.86) pg/105, the ex-pression of Cys-LTs was increased in the control IL-5+15 μg/mL LL-37 sub group (59.97±6.83) pg/105 and the control IL-5+30μg/mL LL-37 sub group (81.44±13.70) pg/105(P<0.05).Compared with the control sub group , the expression of Cys-LTs was in-creased in the asthma 15 μg/mL LL-37 sub group and the asthma 30μg/mL LL-37 sub group ( P<0.05) .Compared with the control LL-37 sub group, the expression of Cys-LTs was decreased in the control PTx sub group , control WRW4 sub group, control suramin sub group, control PTx +LL-37 sub group, and control WRW4+LL-37 sub group (P<0.05).Western blot results indicated that LL-37 treatment induced the activation and phosphorylation of ERK 1/2 in eosinophil, and PTx and WRW4 blocked the upregulation of pERK1/2 induced by LL-37.Treatment with PD inhibited the phosphorylation of cPLA 2 and the release of Cys-LTs induced by LL-37. hCAP18 was higher in the asthma groups than the healthy control . Conclusion LL-37 was identified as an eosinophil-activating pep-tide that could trigger the release of inflammatory mediators , which might be involved in occurrence and development of asthma through regulating ERK1/2 phosphorylation, inducing cPLA2 phosphorylation and finally initiate synthesis of cys-LTs.This suggests that LL-37/hCAP18 and its signaling pathway might be potential therapeutic targets for asthma .
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Abstract Recent studies about the cutaneous barrier demonstrated consistent evidence that the stratum corneum is a metabolically active structure and also has adaptive functions, may play a regulatory role in the inflammatory response with activation of keratinocytes, angiogenesis and fibroplasia, whose intensity depends primarily on the intensity the stimulus. There are few studies investigating the abnormalities of the skin barrier in rosacea, but the existing data already show that there are changes resulting from inflammation, which can generate a vicious circle caused a prolongation of flare-ups and worsening of symptoms. This article aims to gather the most relevant literature data about the characteristics and effects of the state of the skin barrier in rosacea.
Subject(s)
Humans , Skin/physiopathology , Rosacea/physiopathology , Skin/blood supply , Skin Physiological Phenomena , Water Loss, Insensible/physiology , Sebum/physiology , Rosacea/etiology , Dermatitis/physiopathologyABSTRACT
Objective To evaluate the serum level of antimicrobial peptide human cationic antimicrobial protein 18 ( hCAP18 ) in non-small cell lung cancer ( NSCLC ) patients and its auxiliary diagnosis and prognosis value.Methods Case-control study was used.The serum level of hCAP18 was measured by enzyme linked immunosorbent assay ( ELISA) in 50 cases with NSCLC patients of department of thoracic surgery and 50 cases healthy people of department of physical examination from January 2011 to January 2012 in Tongji Hospital of Tongji University.The concentrations of hCAP18 in serum of NSCLC patients before and after surgery were analyzed.The sensitivity and specificity of serum hCAP18 for the diagnosis of NSCLC were evaluated using the receiver operating characteristic ( ROC ) curves.Data was analyzed by using the t-test and Log-rank test.Results Serum hCAP18 concentration in NSCLC patients (6 733 ±771.8) μg/L was significantly higher than in healthy controls (253 ±6.9) μg/L (t=8.396, P390.0μg/L (χ2 =22.64,P<0.05).Conclusions Detection of serum hCAP18 shows a good sensitivity and specificity for the auxiliary diagnosis of NSCLC. It is possible to be a potential detection index for noninvasive diagnosis and monitoring progression of lung cancer.
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Objective To study the effects of antimicrobial peptide LL-37 expressed and purified from prokaryotes on candida albicans growth. Methods (1) Thirty female Kunming mice were treated with estrogen and white candida yeast suspension were poured into vagina to establish a vulvovaginal candidiasis (VVC) murine model. After successful establishing the VVC mouse model, mice were randomly sorted into test group (n=15) and control group (n=15) . Suspension(30μl, 100μg/ml)of recombinant peptide LL-37 expressed and purified in Prokaryotes was given by intravaginal administration to the test group for 5 days, while the same amount of phosphate buffered saline (PBS) was given to the control group. (2) Tweenty-four hours after treatment, the fungal burden and colony-forming unit (CFU) of vaginal fluids were evaluated. All mice were subsequently sacrificed and vaginal tissues were harvested for tissue homogenate preparation. ELISA was used to determine the levels of nterleukin-10(IL-10)and interferon-γ(IFN-γ)in the isolated vaginal tissues. Results (1) VVC mouse model was established successfully in this study. Vaginal mucosa congestion, edema, vaginal plica disappearing were obviously observed in the control group. After treatment with recombinant protein LL-37 vaginal mucosa has no obvious change in the test group. (2) Fungal burden and CFU of vaginal fluids were significantly lower in the test group [(4.8±1.0)×104 CFU/ml] than that in the control group [(8.5 ± 2.1) × 104 CFU/ml, P=0.017]. IFN-γlevel of the test group was increased [(257 ± 11) vs (197 ± 4) pg/ml, P=0.000], while the level of IL-10 was reduced [ (287 ± 15) vs (379 ± 17) pg/ml P=0.000] resulting in a the ratio of IFN-γ/IL-10 was in significantly higher in test group (0.892±0.008 vs 0.496±0.013, P=0.000). Conclusion Recombinant protein LL-37 expressed and purified from prokaryotes inhibits the growth candida albicans and improves vaginal immunity by adjusting IFN-γand IL-10 secretion in the VVC mouse model, highlighting the therapeutic potential of LL-37 for VVC.
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Antimicrobial peptides (AMPs) have a widespread distribution in human body and have antimicrobial activity against microorganisms with wide-range class of host-defense molecules. These are small cationic peptides that play an important role in the development of innate immunity with activity against gram-positive and negative bacteria, parasites, fungi and some viruses. In the oral cavity, the AMPs are produced by the salivary glands and the oral epithelium and serve as defensive purposes. At least forty-five identifiable antimicrobial gene products found in saliva are secreted from oral epithelial cells, salivary glands and neutrophils. AMPs also serve as effective biological molecules in immune response activation, inflammation and wound healing The aim of this review was to discuss the types and functions of oral AMPs and their role in combating microorganisms and infections in the oral cavity. AMPs have a promising potential to be used against oral microbes in order to control their growth and biofilm formation. There are many challenges that need to be overcome in order to design and synthesize AMPs that have the ability to with stand the unique and harsh oral environment. AMPs are expected in the future to be used as models for developing effective oral microbial antibiotics.
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Objective To verify the antibacterial activity of the conserved domain derived from the novel human antimicrobial peptide-hGlyrichin .Methods Bioinformative analysis was performed and two peptides derived from hGlyrichin were synthesized which contained the conserved domain .Results Analysis of antimicrobial activities showed that these two peptides exhibited strong antibacterial activity which was inversely proportional to the length of the peptide within an eligible range.Despite the effective inhibition and killing of bacteria , the synthetic peptide segments had no hemolytic effect on human red blood cells .Conclusion These results indicate that a conserved domain exists in hGlyrichin , and that the peptides which contain this domain have strong antibacterial activity but are not toxic to human somatic cells .
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Objective To explore the effect and its possible mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) on bacterial growth in bronchoalveolar lavage fluid (BALF) of newborns with ventilator associated pneumonia (VAP).Methods Newborns admitted to neonatal intensive care unit (NICU) in Guangdong Women and Children Hospital Affiliated to Guangzhou Medical University from June 1,2012 to December 31,2012 were reviewed.The inclusion criteria were:(1)Positive BALF culture results.(2) Requirement of mechanical ventilation with tracheal intubation.(3) Diagnosed as ventilator-associated pneumonia.Two pieces of BALF samples of newborn were collected and randornaly divided into experimental and control group.hUCMSCs were added into the experimental group,while the same volume of conditioned medium was added into the control group.Both groups were incubated for six hours in humidified CO2 incubator at 37 ℃,then,bacterial growth was assessed by colony forming unit (CFU) counts.Levels of the antimicrobial peptides (Cathelicidin/LL-37 and human HBD-2) were determined by enzyme-linked immunosorbent assay and Western blot.Paired t-test was used for statistical analysis.Results Among the culture results of 31 newborns,there were Klebsiella pneumoniae (6 cases,19.3％),Stenotrophomonas narrow food aeromonas (6 cases,19.3％),Hemolytic staphylococci (5 cases,16.1％),Escherichia coli (3 cases,9.7％),Bacterial meningitis septicemia Elizabeth Platinum (3 cases,9.7％),Acinetobacter baumannii (3 cases,9.7％),Pseudomonas putida (2 cases,6.4％),Pseudomonas aeruginosa (1 case,3.2％),Staphylococcus aureus (1 case,3.2％) and Enterobacter cloacae (1 ease,3.2％).The CFU counts in experimental group were much less than those in control group [(2.60±0.67) ×104] CFU/ml vs [(1.18±0.32) ×105] CFU/ml,(t=-20.19,P＜0.01).Levels of Cathelicidin/LL-37 and HBD-2 in experimental group were higher than those in control group [Cathelicidin/LL-37:(8.98 ± 3.22) ng/ml vs (3.18 ± 1.57) ng/ml,t =17.79,P ＜ 0.01 ;HBD-2:(379.87±11.74) pg/ml vs (39.89±2.86) pg/ml,t=37.62,P＜0.01].Conclusions hUCMSCs had antimicrobial effect on bacterial growth in BALFs from ventilator associated pneumonia possibly by the secretion of antimicrobial peptides (Cathelicidin/LL-37 and HBD-2).
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Objective To evaluate the inhibitory effects on Candida albicans of vagina cells transferred with antimicrobial peptide LL-37 and human defensin 5 (HD5) recombinant plasmids and observe secretion of IL-8.Methods ( 1 ) The epithelial cells from female vagina were culture primarily.The pcDNA3.1 ( + )/HD5-EGFP and pcDNA3.1 ( + )/LL-37-EGFP eukaryotic recombinant plasmids were separately or jointly transferred into the fourth generation of vaginal epithelial cells.Two test groups were defined:one test group was no Candida albicans group including four subgroups which were untransferred group,HD5 group transferred with pcDNA3.1 ( + )/HD5-EGFP,LL-37 group transferred with pcDNA3.1 (+)/LL-37-EGFP,combining transferring group transferred with pcDNA3.1 ( + )/HD5-EGFP and pcDNA3.1 ( + )/LL-37-EGFP; the other test group was with Candida albicans group which the Candida albicans were coincubated with the four subgroups described above.(2) For examination of cytokines and chemokines,at 6,12,24 and 48 hours,the supernatant of every group was collected.ELISA was applied to detect the levels of LL-37,HD5 and IL-8.At each time point,the growth inhibition of Candida albicans was calculated by glucose consumption testing.Results ( 1 ) The max level of LL-37,HD5 and IL-8 reached max level after being transferred for 24 hours,then showed decreasing trend.The secretion of LL-37,HD5 and IL-8 was significant higher in combining transferring group in Candida albicans group than other groups,and the secretion level of LL-37,HD5 and IL-8 was (100.16 ±0.81 ) ng/ml,(58.50 ±2.08) μg/ml and ( 101.03 ± 1.59) pg/ml (P ＜0.01 ).(2) In different time point,the absorbance of each subgroup without Candida albicans declined slowly,and there were no statistically significant difference (P ＞0.05 ),as while as in LL-37 subgroup and HD5 subgroup with Candida albicans.In group with Candida albicans,the absorbance of combining transferring subgroup were 3.210 ± 0.010,3.150 ± 0.030,3.099 ± 0.030 and 2.970 ±0.040 at 6,12,24 and 48 hours,respectively,which was significantly higher than those in the other cells (P ＜ 0.01 ),and the declined trend was the slowest.Conclusions The antifungal ability of vaginal epithelial cell became stronger after being transferred with LL-37 and HD5 recombinant plasmids.LL-37 and HD5 could also possess immunomodulatory activity and induce chemokine IL-8 production.
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Los péptidos antimicrobianos son las moléculas efectoras del sistema inmune innato, cuyas familias se encuentran en casi todos los organismos, desde bacterias hasta mamíferos. Son una familia de sustancias polifacéticascon complejos mecanismos deacción relacionados con la interacción con el patógeno a través de su membrana, o afectando blancos internos, como la replicación del ADN y la síntesis de proteínas, e interactuando con el huésped con funciones inmunomoduladoras de la regulación delproceso inflamatorio y de la cicatrización. Aunque la generación de resistencia a los péptidos antimicrobianos es mucho menorsi se compara con la generada por losantibióticos convencionales, existen mecanismos de resistencia ya descritos, como la degradación por proteasas, la liberación de proteínas inhibidoras o los cambios en la conformación de la membrana externa del patógeno. El estudio de estas sustancias hapermitido evidenciar sus usos potenciales en el ámbito clínico para contrarrestar los inconvenientes de la resistencia a los antibióticos; sin embargo, a pesar de los grandesavances logrados en este campo, aún quedan puntos controversiales por dilucidar.
The antimicrobial peptides (AMP) are theeffectors molecules of the innate immunesystem, finding groups of this kind of substances in almost all living organisms from bacteria to mammals. They are a family of versatile substances with complexes action mechanisms in the pathogen they interact with membrane, DNA synthesis and protein synthesis and folding, and also with the hostshowing immunomodulatory functions inwound healing and inflammation process.Even though the generation of resistance to the AMP is lower compare with conventional antibiotics there are resistance mechanism already describe to this kind of substances like degradation by proteases, releasing ofinhibitory substances or conformationalchanges in the external membrane of thepathogen. Actually the study of this group of substances has make them see as potential tools for clinical use helping to coun-teract the problem of antibiotic resistance, but even great progress had been made in this field there still exist some controversial issues for future study.