Interleukin-22 derived from cervical cancer-associated fibroblasts accelerates senescence of normal fibroblasts and promotes expression of tumorigenesis-related factors in HeLa cells

Abstract

The present study aimed to evaluate the effect of interleukin-22 (IL-22), secreted by cervical cancer-associated fibroblasts (CAFs), on the senescence of normal fibroblasts (NFs) and the malignant characteristics of cancer cells. CAFs and NFs were isolated from clinical tissue samples and the degrees of senescence were compared. NFs were cultured with a CAF-conditioned medium and analyzed for the expression of senescence markers. HeLa cells were cultured with an exogenous IL-22 supplement and analyzed for the expression of tumor markers. Compared to NFs, CAFs showed a delayed growth and an elevated activity of senescence-associated β-galactosidase (SA β-gal). Expression of α-SMA, p16, and IL-22 was upregulated in the CAFs. Further, the CAF-conditioned medium promoted the senescence of NFs through the suppression of cell proliferation and the elevated expression of α-SMA and p16; whereas the addition of an IL-22 antibody reversed the senescence process. Exogenous IL-22 upregulated N-cadherin and downregulated E-cadherin in HeLa cells. The IL-22 supplement also increased the expression of VEGF, MMP2, and MMP9 in HeLa cells. In conclusion, IL-22 produced by CAFs accelerated the senescence of NFs and promoted the expression of tumorigenesis-related factors in HeLa cells.

Current landscape of exosomes in tuberculosis development, diagnosis, and treatment applications

“…Exosomes are expected to serve as key vehicles for MTB pathogen-associated molecular patterns (PAMPs), through which MTB s inhibit host immune responses, and promote immune escape and survival. The dynamic change and balancing tendency of cytokines is a manifestation of immune effect in many immune-related diseases ( 40 – 43 ). MTB conjugated to toll-like receptor 2 (TLR2) triggers mast cells to release exosomes containing high levels of chemokine (C-C motif) ligand 2 (CCL2), IL-4, and IL-13, and causes macrophage M2 polarization, which potentiates the immune escape effect of MTB ( 44 ).…”

Cancer-associated fibroblasts: Origin, function, imaging, and therapeutic targeting

“…FAP [27,28] Fibroblast activation protein TGF-b1 [29][30][31] Transforming growth factor b FGF2 [32] Fibroblast growth factor 2 IL-6 [33][34][35] IL-33 [36] IL-17a [37] IL-22 [38,39] IL-32 [40] Interleukins a-SMA [41] a-Smooth muscle actin CXCL12 [42,43] CXCL1 [44] CXC Chemokine ligand FSP 1 [48] Fibroblast-specific protein MMP-1 [45,46] Matrix metalloproteinases COL11A1 [47,48] Collagen type XI alpha 1 chain LOX [49][50][51] Lysyl oxidase (LOXL) NAB2 [52] NGFI-A-binding protein VEGF [53] Vascular endothelial growth factor NG2 [54] Neural/glial antigen 2 Gal-1 [55] Galectin-1 MFAP5 [56] Microfibril associated protein 5 Chi3L1 [57] Chitinase-3-like protein 1 PDPN [58] Podoplanin HGF [59][60][61] Hepatocyte growth factor ASPN [62] Asporin ANXA1 [63] Annexin A1…”