Mycoplasma genitalium Protein of Adhesion Induces Inflammatory Cytokines via Cyclophilin A-CD147 Activating the ERK-NF-κB Pathway in Human Urothelial Cells

Abstract

Mycoplasma genitalium protein of adhesion (MgPa) plays an important role in the process of adhesion and invasion of host cells by M. genitalium, and is thus significant for its pathogenic mechanisms in host cells. Our previous study has demonstrated that cyclophilin A (CypA) is the receptor for MgPa in human urothelial cells (SV-HUC-1) and can, therefore, mediate the adherence and invasion of M. genitalium into host cells by interacting with MgPa. However, the specific pathogenesis of M. genitalium to host cells and the possible pathogenic mechanism involved in the interaction of MgPa and CypA have never been clarified. The study aimed to elucidate the mechanism involved in the pathogenicity of MgPa. Recombinant MgPa (rMgPa) induced extracellular CypA (eCypA) was detected in SV-HUC-1 cells by ELISA, and the interaction between CypA and CD147 was validated using co-localization and co-immunoprecipitation assay. In addition, both extracellular signal-regulated kinases (ERK) phosphorylation and NF-κB activation evoked by rMgPa-induced eCypA were also demonstrated. The findings of this study verified that rMgPa could induce the secretion of eCypA in SV-HUC-1 cells and thus promote the protein and mRNA expression of IL-1β, IL-6, TNF-α and MMP-9 via CypA-CD147 interaction and thus activating ERK-NF-κB pathway, which is beneficial to elucidate the pathogenesis and possible pathogenic mechanism of M. genitalium to host cells.

Mycoplasma genitalium Protein of Adhesion Promotes the Early Proliferation of Human Urothelial Cells by Interacting with RPL35

“…Our previous study confirmed that cyclophilin A (CypA), the key player for etiological agent's infection, is the receptor protein of MgPa, which can partially inhibit M. genitalium from adhesion and even invasion into human urethral epithelial cells [16,26]. Our previous study also validated that MgPa can stimulate the secretion of CyPA in SV-HUC-1 cells and, thus, promote the expression of inflammatory cytokines through the CyPA-CD147-ERK-NF-κB signal pathway [27]. However, the specific MgPa protein may have many different interacting proteins.…”

The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

“…Specifically, the stimulation of CD147 leads to the activation of mitogen-activated protein kinases (MAPK)/extracellular-regulated kinases (ERK) and the phosphoinositide 3 kinase (PI3K)/AKT intracellular signaling pathways [ 43 , 60 , 61 , 62 , 63 , 64 , 65 ], which will then turn on transcriptional activators of MMP expression such as Nuclear Factor-kappa B (NF-kB), Activator Protein (AP)-1, Specificity protein (Sp)-1, and E26 transformation-specific (ETS) factor ( Figure 1 ) [ 66 , 67 , 68 , 69 , 70 , 71 ].…”

Current update on theranostic roles of cyclophilin A in kidney diseases

“…Another study has also reported that eCyPA binds CD147, resulting in activation of ERK1/2 and p38 MAPK signaling pathways and cell proliferation 35 . In concordance, an adhesion molecule secreted from Mycoplasma genitalium can induce secretion of eCyPA and its interaction with CD147 on urothelial cells, resulting in activation of extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-κB pathway 36 . As a result, cellular inflammatory response occurs together with production and release of proinflammatory cytokines and mediators, e.g., interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) 36 .…”

“…In concordance, an adhesion molecule secreted from Mycoplasma genitalium can induce secretion of eCyPA and its interaction with CD147 on urothelial cells, resulting in activation of extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-κB pathway 36 . As a result, cellular inflammatory response occurs together with production and release of proinflammatory cytokines and mediators, e.g., interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) 36 . Altogether, the accumulated evidence strengthens the role of eCyPA to evoke the inflammatory response.…”