Cathelicidin (LL-37) and its correlation with pro-oxidant, antioxidant balance and disease activity in systemic lupus erythematosus: a cross-sectional human study

Abstract

Background Cathelicidin (LL-37), an endogenous antimicrobial peptide, has recently been involved in the pathogenesis of autoimmune diseases. To assess whether LL-37 reflects disease activity, we measured serum levels of it in systemic lupus erythematosus (SLE) patients with active and inactive disease compared to healthy controls. LL-37 was also compared between new and old cases. Moreover, the correlation of LL-37 and pro-oxidant, antioxidant balance (PAB) was measured. Methods The study population consisted of 50 SLE patients and 28 healthy controls. Of those, 39 patients had active and 11 patients had inactive disease. Serum levels of LL-37 were measured by ELISA and PAB values by a special method. Results There was no difference in levels of LL-37 between patients and healthy controls (50.9 ± 20.8 vs. 67.7 ± 43.3 ng/ml, P = 0.31). LL-37 did not correlate with SLEDAI and its items in total patients. LL-37 had a positive correlation with SLEDAI in active patients ( P = 0.01, r = 0.4). In active patients (78% of patients), multivariate regression analysis showed significant negative correlation between LL-37 and C3 ( P = 0.01, standardized beta -0.50). No difference was found in levels of PAB between patients and controls (90.4 ± 34.1 vs. 86.9 ± 25.6 HK, P = 0.4).There was no difference in the levels of PAB between patients with active and inactive disease (93.2 ± 34.1 vs. 80.2 ± 33.7 HK, P = 0.27). No correlation was found between levels of PAB and SLEDAI items and total score. However, a positive correlation between the levels of LL-37 and PAB in SLE patients was found ( r = 0.3, P < 0.01). Conclusion Based on this study, serum LL-37 and PAB did not increase in lupus compared with healthy individuals. LL-37 serum values rose in parallel with SLEDAI in active disease. Positive correlation between serum PAB and LL-37 could be a great achievement of this study that may suggest the role of antioxidants in controlling NETosis.

Cathelicidin LL-37: A new important molecule in the pathophysiology of systemic lupus erythematosus

“…Although, the in vitro role of LL-37 in SLE pathogenesis has been demonstrated; in vivo LL-37 serum measures by EIA are not conclusive. Some studies show a lack of association between LL-37 and disease activity or organic compromise [ 46 , 47 ], without this association being altered by other variables such as age, sex or duration of the disease; though higher levels of LL-37 have been associated with presence of chronic cutaneous lupus erythematosus [ 48 , 49 ]. However, the inconsistency in findings warrants additional studies to investigate whether LL-37, which may have a biological role in SLE pathogenesis, could serve as a marker of lupus activity.…”

A cathelicidin-related antimicrobial peptide suppresses cardiac hypertrophy induced by pressure overload by regulating IGFR1/PI3K/AKT and TLR9/AMPKα

“…The antimicrobial peptide cathelicidin (CRAMP in mouse/rat, LL-37 in human) is expressed in many immune cells, such as epithelial cells, and genital cells 10 . CRAMP was initially reported as an immunomodulatory peptide that functions in many autoimmune diseases, such as psoriasis 11 , systemic lupus erythematous 12 , arthritis 13 , atherosclerosis 14 , and type 1 diabetes 15 . Recent studies have identified a role of CRAMP in cardiovascular disease.…”

Functional Implications of Cathelicidin Antimicrobial Protein in Breast Cancer and Tumor-Associated Macrophage Microenvironment

“…CAMP is constitutively expressed in neutrophils, natural killer (NK) cells, dendritic cells, monocytes, and especially macrophages [42][43][44][45]. It has been widely accepted that CAMP has an important role in inflammatory-related diseases such as chronic inflammatory skin disease [38], Crohn's disease [46], and autoimmune diseases including psoriatic arthritis [47], systemic lupus erythematosus [48], and atherosclerosis [49]. Apart from its antimicrobial function, CAMP has also been reported to regulate a wide range of activities including apoptosis, cell proliferation, angiogenesis, and wound healing [37,50].…”