Nicotine causes alternative polarization of macrophages via Src‐mediated STAT3 activation: Potential pathobiological implications

Abstract

Nicotine is an addictive ingredient of tobacco products and other noncigarette substitutes, including those being used for smoking cessation to relieve withdrawal symptoms. Earlier research, however, has associated nicotine with the risk and poorer outcome of several diseases, including cancer. Macrophages are an important component of the innate immune system and can have both pro-and antiinflammatory functions depending upon their polarization state. Here, we investigated the effect of nicotine on macrophage polarization, growth, and invasion to understand its role in human physiology. We observed that nicotine induced M2 polarization of RAW264.7 and THP-1-derived macrophages in a dose-dependent manner. Cytokine profiling suggested a mixed M2a/d phenotype of nicotinepolarized macrophages associated with tissue repair and pro-angiogenic functions.Moreover, nicotine treatment also enhanced the growth, motility, and invasion of macrophages. Mechanistic studies revealed increased phosphorylation of STAT3 in nicotine-treated macrophages that was mediated through Src activation. Importantly, pretreatment of macrophages with either Src or STAT3 inhibitor abrogated nicotine-induced macrophage polarization, growth, and motility, suggesting a functional role of the Src-STAT3 signaling axis. Together, our findings reveal a novel role of nicotine in immunosuppression via causing M2 polarization of macrophages that could be implicated in the pathogenesis of various diseases.

Biphasic transcriptional and posttranscriptional regulation of MYB by androgen signaling mediates its growth control in prostate cancer

“…The cell growth assay was performed as described previously ( 50 ). Briefly, cells (1 × 10 4 /well) were seeded in 96-well plates for 24 h. Thereafter, media was replaced by CSS containing fresh media and allowed to grow for 24 h. Cells were then treated with different concentrations (0–100 nM) of DHT for different time intervals (48–96 h), and cell growth was measured using WST-1 assay.…”

The immunomodulatory effect of oral NaHCO3 is mediated by the splenic nerve: multivariate impact revealed by artificial neural networks

“…Accordingly, VNS, an established IR activator, reduces neutrophil migration [ 36 ], promotes microglial M2-like polarization [ 15 ], and reduces lung mRNA levels of M1-like macrophage markers, while increasing M2-like markers [ 44 ]. Furthermore, nicotine, another IR activator, reduces neutrophil recruitment during sepsis development [ 36 ], and induces both anti-inflammatory macrophage polarization [ 73 ] and Tregs number [ 52 ].…”

RIG-I agonist SLR10 promotes macrophage M1 polarization during influenza virus infection

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