Exogenous murine antimicrobial peptide CRAMP significantly exacerbates Ovalbumin-induced airway inflammation but ameliorates oxazolone-induced intestinal colitis in BALB/c mice

Abstract

Cathelicidin has been reported to be multifunctional. The current study aimed to investigate the influences of exogenous cathelicidin-related antimicrobial peptide (CRAMP) on inflammatory responses in different disease models. In OVA-induced allergic airway inflammation, CRAMP significantly enhanced the infiltration of inflammatory cells and accumulation of proinflammatory Th2 cytokine IL-13 and IL-33 in bronchial alveolar lavage fluid (BALF), exacerbated lung tissue inflammation and airway goblet cell hyperplasia, and elevated OVA-specific IgE level in serum. In oxazolone-induced intestinal colitis, the expression levels of CRAMP and its receptor FPR2 significantly increased in comparison with those of TNBS-induced mice, vesicle and normal controls. Exogenous CRAMP significantly prevented the development of ulcerative colitis, evidenced by improved body weight regain, decreased colons weight/length ratio, elevated epithelial integrity, and ameliorated colon tissue inflammation. In addition, pro-inflammatory cytokines TNF-α, IL-1β, IL-4 and IL-13, as well as chemokines CXCL2 and CXCL5 for neutrophils recruitment were significantly decreased in CRAMP-treated mice, and epithelial repair-related factors MUC2 and Claudin1 were increased, determined by real time-PCR and ELISAs. The results indicated that although CRAMP has pro-inflammatory effects in airway, local application of exogenous CRAMP might be a potential approach for the treatment of ulcerative colitis.

Host Cathelicidin Exacerbates Group BStreptococcusUrinary Tract Infection

“…Mast cell activation by LL-37 is thought to act through the MrgX2 receptor, a G protein-coupled receptor (GPCR), but other receptors, including FPRL1 and P2X7, have been proposed (88). The proinflammatory functions of cathelicidin have been observed in many human diseases and mouse inflammatory models (51,(89)(90)(91)(92), and this capacity to enhance tissue inflammation is consistent with the observations in our study. Interestingly, in the absence of cathelicidin, we saw an enhancement of neutrophil MPO release (Fig.…”

Egg Protein Transferrin-Derived Peptides IRW and IQW Regulate Citrobacter rodentium-Induced, Inflammation-Related Microbial and Metabolomic Profiles

“…The results of mouse experiments showed that porcine β-defensin 2 might improve mucosal lesions and extracellular permeability by targeting the NF-κB pathway and could thus alleviate inflammatory enteritis (Han et al, 2015). Cathelicidin-related antimicrobial peptide (CRAMP) restore body weight loss caused by ulcerative colitis and maintain colonic epithelial integrity (Li et al, 2018). Cathelicidin-BF can effectively inhibit the phosphorylation of NF-κB and increase the intestinal barrier function to reduce inflammation (Zhang H. et al, 2015).…”

Cryptosporidium parvum Subverts Antimicrobial Activity of CRAMP by Reducing Its Expression in Neonatal Mice

“…As previously described [ 20 ], the first oocysts were found in the intestine 4 days post-inoculation (dpi) and the peak of infection was reached at 9 dpi. Surprisingly, whereas CRAMP expression is often described to be strongly upregulated under inflammatory conditions [ 18 , 22 , 23 ], it was significantly downregulated upon infection by C. parvum. The stronger mRNA downregulation was observed in the intestine at day 9 dpi ( Figure 1 C left panel).…”