Abstract
The M1 and M2 states of macrophage are the two extremes of a physiologic/phenotypic continuum that is dynamically influenced by environmental signals. Molecular mechanism analysis indicated that they gain M1 and M2-related functions after encountering specific ligands in the tissue environment. Here, we first characterized the previously unknown immunobiological functions of mouse Tmem106a. This protein is abundantly expressed on the surface of mouse macrophages. Activation of Tmem106a by stimulation with anti-Tmem106a upregulated the expression of CD80, CD86, CD69 and MHC II on macrophage, and induced the release of TNF-α, IL-1β, IL-6, CCL2 and NO, but not IL-10. These effects were largely abrogated by pretreatment with siRNA against Tmem106a. Notably, anti-Tmem106a significantly increased iNOS production and phosphorylation of STAT1, and had no effect on the ARGINASE-1 or p-STAT6 level, indicating that anti-Tmem106a activated macrophages and polarized them into M1-like macrophages. Further analysis found that anti-Tmem106a stimulation increased phosphorylation of ERK-1/2, JNK, p38 MAPK, NF-κB p65 and IKKα/β, and promoted nuclear translocation of the cytosolic NF-κB p65 subunit. Collectively, these data suggest that mouse Tmem106a might be a new trigger of macrophage activation and have some influence toward the M1 state through the activation of the MAPKs and NF-κB pathway.
Highlights
Monocytes and tissue macrophages provide both immediate defense against foreign agents and assist during the initiation and development of the adaptive immune response
No functional studies have been performed on this protein
We examined the secretion of nitric oxide (NO) which is a hallmark of M1 macrophages, in the culture supernatant of mouse peritoneal macrophage (PMp) using a nitrite detection method
Summary
Monocytes and tissue macrophages provide both immediate defense against foreign agents and assist during the initiation and development of the adaptive immune response. Diversity and plasticity are hallmarks of these cells They can rapidly change their function in response to local microenvironmental signals[1]. Activated M2 macrophages are considered to be involved in anti-inflammatory activity, promotion of tissue remodeling, tumor progression, and to have immunoregulatory functions[2,4,5,6]. The effector function of macrophages is controlled by specific triggering signals such as cytokines, glucocorticoids and catecholamines, which stimulate differentiation into M1 or M2 macrophages[2,8,9,10,11]. Human TMEM106C is a differentially expressed transcript in ankylosing spondylitis (AS)[20], and porcine TMEM106C was a positional and functional candidate for arthrogryposis multiplex congenita (AMC)[21]
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