Collagen Synthesis Is Suppressed in Dermal Fibroblasts by the Human Antimicrobial Peptide LL-37

Abstract

LL-37 is a human cathelicidin antimicrobial peptide that is released in the skin after injury and acts to defend against infection and modulate the local cellular immune response. We observed in human dermal keloids that fibrosis was inversely related to the expression of cathelicidin and sought to determine how LL-37 influenced expression of types I and III collagen genes in dermal fibroblasts. At nano-molar concentrations, LL-37 inhibited baseline and transforming growth factor-β-induced collagen expression. At these concentrations, LL-37 also induced phosphorylation of extracellular signal-regulated kinase (ERK) within 30 minutes. Activation of ERK, and the activation of a G-protein-dependent pathway, was essential for inhibition of collagen expression as pertussis toxin or an inhibitor of ERK blocked the inhibitory effects of LL-37. c-Jun N-terminal kinase and p38 mitogen-activated protein kinase inhibitors did not alter the effects of cathelicidin. Silencing of the Ets-1 reversed inhibitory effects of LL-37. Taken together, these findings show that LL-37 can directly act on dermal fibroblasts and may have antifibrotic action during the wound repair process.

Acute ST-Segment Elevation Myocardial Infarction is Associated with Decreased Human Antimicrobial Peptide LL-37 and Increased Human Neutrophil Peptide-1 to 3 in Plasma

“…In addition, some inflammatory markers, such as IL-10, are modulators for healing and repair of the infarcted myocardium, and promoting more effective tissue repair may reduce deleterious remodeling, which is the leading cause of heart failure and death after AMI 27) . As LL-37 is involved in tissue healing and repair [18][19][20] , plasma LL-37 levels may be useful for predicting future cardiac events related to remodeling. Furthermore, the combination of blood HNP1-3 and LL-37 measurement, or together with other blood parameters, such as CRP, is possibly a multi-biomarker strategy for prognosis in patients with myocardial infarction.…”

“…Thus, the divergence between local and systemic LL-37 levels detected in STEMI is probably due to flow cessation by sudden total coronary artery occlusion, which tem- has beneficial effects. Park et al 18) reported that LL-37 protein expression was lower in keloid tissue than in normal skin and LL-37 inhibited collagen production in human dermal fibroblasts, suggesting that LL-37 may have antifibrotic action during the wound repair process. LL-37 may also induce fibroblast proliferation, which contributes to tissue repair 19) .…”

LL-37 attenuates inflammatory impairment via mTOR signaling-dependent mitochondrial protection

“…Skin TMA sections (Cybrdi, Shanxi ChaoYing, Xi'an, China), which included 80 samples (12 squamous cell carcinoma, 12 basal cell carcinoma, 12 malignant melanoma, 10 condyloma acuminatum, 6 basal cell papilloma, 1 cyst, 1 verruca vulgaris, 6 hyperplasia, 5 chronic inflammation, 5 cancer-adjacent tissue, 5 cancer-adjacent normal dermatic tissue, and 5 normal dermatic tissue) were assayed as previously described (Park et al, 2008) (Table 2). Briefly, the anti-LL-37 primary antibody (Santa Cruz Biotechnology, Santa Cruz, CA) was applied followed by the Polink-2 plus ® polymer HRP detection system (Zhongshan Jinqiao, Beijing, China).…”

The role of the ERK1/2 signalling pathway in the pathogenesis of female stress urinary incontinence

“…The activity of the ERK1/2 pathway is regulated by many different stimuli, including growth factors, cytokines, viral infection, transforming agents and carcinogens, which can then influence collagen synthesis. [26][27][28] In conclusion, female SUI is associated with reduced levels of p-ERK1/2 compared with controls, and inhibition of the ERK1/2 signalling pathway inhibits collagen types I and III synthesis in vaginal wall fibroblasts. It is possible that abnormalities in ERK1/2 activation may be involved in the pathogenesis of female SUI.…”