Hydrogen sulfide of air induces macrophage extracellular traps to aggravate inflammatory injury via the regulation of miR-15b-5p on MAPK and insulin signals in trachea of chickens

Hydrogen sulfide (H2S) is an environmental contaminant to cause the airway damage. The release of macrophage extracellular traps (METs) is the mechanism of immune protection to harmful stimulation via microRNAs, but excessive METs cause the injury. However, few studies have attempted to interpret the mechanism of an organism injury due to H2S via METs in chickens. Here, we investigated the transcriptome profiles, pathological morphologic changes and METs release from chicken trachea after H2S exposure. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 10 differentially expressed genes were related to the METs release, the MAPK and insulin signaling pathways. Morphological and immunofluorescence analysis showed that H2S caused airway injury and MET release. H2S activated the targeting effect of miRNA-15b-5p on activating transcription factor 2 (ATF2). Western blotting and real time quantitative PCR results showed that H2S down-regulated the levels of dual specificity protein phosophatase1 (DUSP1) but up-regulated p38 MAP Kinase (p38) in the MAPK signal pathway. And the expression of phosphoinositide-dependent protein kinase 1 (PDK1), serine/threonine kinase (Akt), and protein kinase ζ subtypes (PKCζ) in the insulin signal pathway were increased after H2S exposure. These promoted the release of myeloperoxidase (MPO) and degradation histone 4 (H4) to induce the release of METs. Taken together, miR-15b-5p targeted ATF2 to mediate METs release, which triggered trachea inflammatory injury via MAPK and insulin signals after H2S exposure. These results will provide new insights into the toxicological mechanisms of H2S and environmental ecotoxicology. [Display omitted] •H2S induced the release of macrophages extracellular traps (METs) in chickens.•H2S triggered METs by p38/PDK1/AKT/PKCζ signaling via miR-15b-5p targeting ATF2.•The release of METs induced by H2S promoted inflammatory injury in chickens.