Involvement of PI3K/AKT and MAPK Pathways for TNF-α Production in SiHa Cervical Mucosal Epithelial Cells Infected with <i>Trichomonas vaginalis</i>

Abstract

Trichomonas vaginalis; induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in TNF-α production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased TNF-α production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, TNF-α production was significantly decreased compared to the control; however, TNF-α reduction patterns were different depending on the type of PI3K/MAPK inhibitors. TNF-α production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of TNF-α production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways

“…Reportedly, C5a can trigger MAPK activation in some target cells [ 41 – 43 ] and MAPK signal pathways are involved in mediating cellular IL-6 and TNF-α production [ 41 , 44 – 47 ]. As a result, the regulatory roles of MAPK signaling pathways in C5a-induced IL-6 and TNF-α expression in the GMC were further explored in the present studies.…”

Trichomonas vaginalis Induces Production of Proinflammatory Cytokines in Mouse Macrophages Through Activation of MAPK and NF-κB Pathways Partially Mediated by TLR2

“…Previous studies also implicated that T. vaginalis infection induced inflammatory responses in epithelial ( Yang et al, 2015 ), neutrophils ( Ryu et al, 2004 ), and macrophages ( Han et al, 2009 ). Proinflammatory cytokines such as IL-6 from human prostate epithelial cells and TNF-α from rat peritoneal mast cells have been demonstrated to be necessary for the T. vaginalis control and the initiation of subsequent adaptive immune response in the process of T. vaginalis infection ( Im et al, 2011 ; Han et al, 2016 ).…”

“…The GPI from parasite could lead the activation of MAPK and NF-κB signal pathways via TLR2 ( Gowda, 2007 ). Human macrophages and SiHa Cervical Mousosal Epithelial cells infected with T. vaginalis increased the activity of phospho NF-κB p65 and p38, ERK, and JNK, respectively ( Han et al, 2009 ; Yang et al, 2015 ). HeLa cells treated with T. vaginalis showed significant up-regulation of TLR2, TLR4, TLR9, which was a p38 MAPK signaling pathway dependent process ( Medzhitov, 2001 ).…”

Silencing LncRNA AK139328 protects vascular endothelial cells from ischemia-reperfusion injury by increasing PI3K/Akt signaling

“…Endothelial progenitor cells (EPCs) are inhibited by TNF-α, but impaired EPCs proliferation is reversed by berberine via the PI3K/Akt/eNOS signaling pathway [28]. Jung et al showed that pre-treatment with PI3K inhibitors decreased TNF-α levels in EPCs [29]. TNF-α-induced inflammation is inhibited by downregulation of the PI3K/Akt signaling pathway in human umbilical vein endothelial cells [30].…”