Calcium-Based Antimicrobial Peptide Compounds Attenuate DNFB-Induced Atopic Dermatitis-Like Skin Lesions via Th-Cells in BALB/c Mice

Int J Mol Sci. 2022 Sep 26;23(19):11371. doi: 10.3390/ijms231911371.

Abstract

Atopic dermatitis (AD) is a chronic and recurrent inflammatory skin disease, characterized by severe itching and recurrent skin lesions. We hypothesized that a novel treatment involving calcium-based antimicrobial peptide compounds (CAPCS), a combination of natural calcium extracted from marine shellfish, and a variety of antimicrobial peptides, may be beneficial for AD. We established a dinitrofluorobenzene (DNFB)-induced AD model in BALB/c mice to test our hypothesis. We observed mouse behavior and conducted histopathological and immunohistochemical analyses on skin lesions before and after CAPCS treatment. We also characterized the changes in the levels of cytokines, inflammatory mediators, and Toll-like receptors (TLRs) in plasma and skin lesions. The results showed that (i) topical application of CAPCS ameliorated AD-like skin lesions and reduced scratching behavior in BALB/c mice; (ii) CAPCS suppressed infiltration of inflammatory cells and inhibited the expression of inflammatory cytokines in AD-like skin lesions; (iii) CAPCS reduced plasma levels of inflammatory cytokines; and (iv) CAPCS inhibited TLR2 and TLR4 protein expression in skin lesions. Topical application of CAPCS exhibits a therapeutic effect on AD by inhibiting inflammatory immune responses via recruiting helper T cells and engaging the TLR2 and TLR4 signaling pathways. Therefore, CAPCS may be useful for the treatment of AD.

Keywords: BALB/c mice; atopic dermatitis; calcium-based antimicrobial peptides compounds; cytokines.

MeSH terms

  • Animals
  • Antimicrobial Peptides
  • Calcium / pharmacology
  • Cytokines / metabolism
  • Dermatitis, Atopic* / chemically induced
  • Dermatitis, Atopic* / drug therapy
  • Dinitrofluorobenzene / pharmacology
  • Inflammation Mediators / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Skin / pathology
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4 / therapeutic use

Substances

  • Antimicrobial Peptides
  • Cytokines
  • Inflammation Mediators
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Dinitrofluorobenzene
  • Calcium