The effect of human antibacterial peptide LL-37 in the pathogenesis of chronic obstructive pulmonary disease

Jiang, Yuanyuan; Xiao, Wei; Zhu, Man; Yang, Zhihua; Pan, Xiujie; Zhang, Yi; Sun, Congcong; Xing, Ying

doi:10.1016/j.rmed.2012.08.018

Cited by 45 publications

(63 citation statements)

References 33 publications

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“…LL-37 and small airway remodeling C Sun et al 16HBE cells with different concentrations of CSE and found that CSE leads to a significant elevation of LL-37 in 16HBE cells, which is in accordance with our previous study that CSE enhanced LL-37 expression in human bronchial epithelial cells and alveolar epithelial cells. 20 Similarly, a-defensin was also reported to be induced by CSE in human alveolar epithelial cells and gingival epithelial cells, 32,33 indicating a potential effect of cigarette smoke on AMP's expression in epithelial cells.…”

Section: Discussionmentioning

confidence: 95%

“…30 Furthermore, increasing body of literature demonstrates that the remodeling processes of the small airways may attribute to excessive production of growth factors by airway epithelium. 4,31 Based on the previous findings that LL-37 levels in small airway epithelium of COPD patients were significantly higher than control subjects, 20 we began to investigate whether epithelial production of LL-37 was involved in small airway remodeling in COPD. In line with our previous findings, a marked upregulation of LL-37 expression was observed in small airways from COPD smokers compared with nonsmokers and smokers without COPD.…”

Section: Discussionmentioning

confidence: 99%

“…RT-PCR was carried out to evaluate the RNA transcriptional levels of COL1A1 and COL3A1, and mRNA levels were assessed using C T values. In our study, C T values for target and control genes are as follows: type I collagen gene (COL1A1) (median, 21; range, [20][21][22], type III collagen gene (COL3A1) (median, 22; range, 21-23), and GAPDH (median, 14; range, 13-15). Relative gene expression was calculated according to the 2 À DDC T method.…”

Section: Ll-37 Increased Collagen Protein and Gene Expression In Humamentioning

confidence: 94%

“…20 Tissue sections were deparaffined and stained with rabbit anti-LL-37 antibody (Abcam, Cambridge, MA, USA) at 1:300 dilution. After incubation to horseradish peroxidase (HRP)-conjugated anti-rabbit antibody (1:1000, ZhongShan Biotech, Beijing, China), color was developed using diaminobenzidine.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…[17][18][19] In addition, our previous study observed a significant increase of LL-37 in airway epithelium from COPD patients and demonstrated that LL-37 was implicated in the pathogenesis of airway inflammation and airway mucus overproduction. 20,21 However, there is no evidence that LL-37 secreted by epithelium is involved in small airway remodeling in COPD. Recently, LL-37 has been reported to show a tendency for increased expression of the alpha 1(I) collagen gene (COL1A1) in human dermal fibroblasts at higher concentrations, 22 whereas the effect of LL-37 on collagen production in human lung fibroblasts has not been explored.…”

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confidence: 99%

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LL-37 secreted by epithelium promotes fibroblast collagen production: a potential mechanism of small airway remodeling in chronic obstructive pulmonary disease

Sun

Zhu

Yang

et al. 2014

Laboratory Investigation

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Emerging evidence suggests that the process of small airway remodeling is mediated by profibrotic growth factors produced by epithelium, which are capable of activating the underlying mesenchymal cells with excessive collagen production. It has been demonstrated that human cathelicidin antimicrobial protein LL-37 is highly expressed in small airway epithelium from COPD patients. However, it is unknown whether the increased levels of LL-37 in epithelium are involved in the pathogenesis of small airway remodeling in COPD. In this study, we examined the expression of LL-37 in small airways from smokers with COPD and controls (non-smokers and smokers without COPD) by immunohistochemistry, and then the association between LL-37 expression in epithelium and the structural changes of small airway remodeling was analyzed. In vitro, the effect of CSE-induced epithelial secretion of LL-37 on collagen production in human lung fibroblasts (HFL-1 cell line) was studied in a co-culture system. Finally, the signaling pathways involved in the effect of LL-37 on fibroblast collagen production were evaluated. The results showed that LL-37 immunoreactivity in airway epithelium was significantly elevated in smokers with COPD compared with controls. In addition, the magnitude of LL-37 expression in epithelium was positively correlated with airway wall thickness and collagen deposition. In vitro, CSE-induced epithelial secretion of LL-37 promoted fibroblast collagen production. Finally, we showed that formyl peptide receptor-like 1 (FPRL1)-dependent extracellular signal-regulated kinase (ERK) signaling pathway was essential for LL-37-induced collagen production in HFL-1 cells. These results suggest that after cigarette smoke exposure, the increased levels of LL-37 in airway epithelium could stimulate collagen production in the underlying lung fibroblasts and may contribute to small airway remodeling in COPD.

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Section: Discussionmentioning

confidence: 95%