The anti-inflammatory regulation of calcitonin gene-related peptide in mouse Aspergillus fumigatus keratitis.
Ontology highlight
ABSTRACT: AIM:To analyze the impact of calcitonin gene-related peptide (CGRP) in mouse keratitis after Aspergillus fumigatus (A. fumigatus) infection. METHODS:C57BL/6 mice were treated subconjunctivally with different concentrations of exogenous CGRP, and BALB/c mice were treated with CGRP8-37 (a CGRP antagonist) before corneas were infected with A. fumigatus. The cornea was assessed under the slit-lamp and the clinical score was recorded. The mRNA levels of IL-1?, TNF-?, IL-6, and MIP-2 were detected by quantitative real-time polymerase chain reaction (PCR), while the protein level of IL-1? was determined by Western blotting. In vitro, RAW264.7 cells were used to investigate NLRP3 and IL-1? expression induced by A. fumigatus after the pretreatment of exogenous CGRP or CGRP8-37. Cytokines expression in RAW264.7 cells was evaluated by real-time PCR and Western blotting. RESULTS:Using exogenous CGRP resulted in down-regulated synthesis of IL-1? and MIP-2 stimulated by A. fumigatus in C57BL/6 mice keratitis, and the synthesis of IL-1?, MIP-2 and IL-6 was up-regulated in BALB/c mice corneas after the pretreatment with CGRP8-37. Pretreatment with exogenous CGRP and CGRP8-37 did not influence TNF-? mRNA levels either in BALB/c or C57BL/6 mice keratitis. The levels of NLRP3 and IL-1? were both reduced in A. fumigatus stimulated-macrophages after treatment with exogenous CGRP. And CGRP8-37 pretreatment would increase NLRP3 and IL-1? levels. CONCLUSION:CGRP may alleviate the inflammatory reaction in mice keratitis after infection with A. fumigatus. The anti-inflammatory effect may be related to the inhibition of NLRP3 expression by CGRP.
SUBMITTER: Xu M
PROVIDER: S-EPMC7201344 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
ACCESS DATA