Substance P increases STAT6-mediated transcription activation of LCP2 to sustain M2 macrophage predominance in pediatric asthma

This study investigates the effect of SP on macrophage phenotype in pediatric asthma and the underpinning factors. Asthmatic children exhibited an increased level of SP, along with a higher proportion of M2 macrophages in their bronchoalveolar lavage fluid (BALF). Flow cytometry revealed that SP treatment enhanced the M2 polarization of TPA-treated THP-1 cells (macrophages) in vitro. By contrast, the administration of a neutralizing antibody of SP reduced the M2 macrophage population, mitigated inflammatory cell infiltration in mouse lung tissues, and decreased the population of immune cells in the mouse BALF. SP upregulated the expression of signal transducer and activator of transcription 6 (STAT6), which in turn activated the transcription of lymphocyte cytosolic protein 2 (LCP2). The population of macrophages and allergic inflammatory responses in mice were reduced by STAT6 inhibition but restored by LCP2 overexpression. Collectively, the present study demonstrates that SP sustains M2 macrophage predominance and allergic inflammation in pediatric asthma by enhancing STAT6-dependent transcription activation of LCP2.PMID:37995836 | DOI:10.1016/j.ajpath.2023.11.003
Source: Am J Pathol - Category: Pathology Authors: Source Type: research