Identification of interleukin-1β regulated genes in uterine smooth muscle cells

Abstract

We analyzed the response of uterine smooth muscle cells to interleukin-1b (IL-1b). We first showed that PHM1-31 myometrial cells, our cellular model, are contractile. To determine the molecular mechanisms of uterine smooth muscle cell activation by proinflammatory cytokines, we performed genechip expression array profiling studies of PHM1-31 cells in the absence and the presence of IL-1b. In total, we identified 198 known genes whose mRNA levels are significantly modulated (O2.0-fold change) following IL-1b exposure. We confirmed the expression changes for selected genes by independent mRNA and protein analysis. The group of genes induced by IL-1b includes transcription factors and inflammatory response genes such as nuclear factor of k light polypeptide gene enhancer in B-cells (NFkB), pentraxin-related gene (PTX3), and tumor necrosis factor a-induced protein 3/A20 (TNFAIP3/A20). We also found up-regulation of chemokines like C-X-C motif ligand 3 (CXCL3) and extracellular matrix remodeling signaling molecules like tenascin C (TNC). Our data suggest that IL-1b elicits the rapid activation of a cellular network of genes particularly implicated in inflammatory response that may create a cellular environment favorable for myometrial cell contraction. Our results provide novel insights into the mechanisms of uterine smooth muscle cell regulation and possibly infection-induced preterm labor.

Plasma PTX3 protein levels inversely correlate with insulin secretion and obesity, whereas visceral adipose tissue PTX3 gene expression is increased in obesity

“…In fact, a positive effect of both IL-1 and TNF␣ has been observed previously in a wide range of cells: endothelial (9,20) and hepatic cells (9), fibroblasts (9,20,23), myoblasts (20), mononuclear phagocytes (3,20), and renal epithelial cells (32). Furthermore, IL-1 was effective in dendritic (12) and smooth muscle cells (11) and TNF␣ in 3T3-F442A adipocytes (1), synoviocytes (26), and lung epithelial cells (17). Similarly, IL-6 did not regulate PTX3 mRNA in endothelial, hepatic, or fibroblastic cells (9), mononuclear phagocytes (3), renal epithelial cells (32), or synoviocytes (26).…”

“…Indeed, PTX3 has different cell-specific gene expression and ligand-binding properties from CRP (8). PTX3 is produced in response to proinflammatory signals by mononuclear phagocytes (3,20), myeloid dendritic cells (12), fibroblasts (9,20,23), endothelial cells (9,20), hepatic cells (9), myoblasts (20), synoviocytes (26), lung epithelial cells (17), renal epithelial cells (32), adipocytes (1), AT-derived mesenchymal stem cells (25), and smooth muscle cells (11). Expression of the PTX3 gene increases in human cultured myotubes compared with the skeletal muscle tissue (38).…”

Sterile inflammation and pregnancy complications: a review

“…(1) stimulation of IL-1R induces the transcription of numerous pro-labor genes via MAPK p38, JNK, c-jun and small GTPase Rho in myometrial smooth muscle cells, which results in increased myometrial contractility (Tribe et al 2003, Chevillard et al 2007, Nadeau-Vallee et al 2015b; and preterm labor in mice and non-human primates (Romero et al 1991, Sadowsky et al 2006; (2) antagonism of IL-1R prevents all of these events (Romero & Tartakovsky 1992, Nadeau-Vallee et al 2015b; (3) IL-1α amniotic fluid levels are elevated in women that deliver preterm (Figueroa et al 2005); (4) preterm labor is associated with increased IL-1α activity in amniotic fluids (Romero et al 1989); and (5) maternal polymorphisms and haplotypes in the IL-1α gene (Sata et al 2009), as well as fetal polymorphism in the endogenous IL-1R antagonist (Witkin et al 2003), have been associated with increased risk of preterm birth. The critical role of IL-1 in preterm labor has been reviewed elsewhere (Nadeau-Vallee et al 2015a).…”

Small Maf Proteins in Mammalian Gene Control: Mere Dimerization Partners or Dynamic Transcriptional Regulators?

“…In contrast, MafG and MafK mRNA and protein expression are not induced rapidly by these cytokines, hinting at a specific role for MafF in the early inflammatory response. 25,106 Of interest, Nrf2 may also be involved in the regulation of inflammation in vivo. [107][108][109][110] It has been shown that Nrf2 functions downstream of prostaglandins regulating the expression of anti-oxidative stress genes during the acute inflammatory response.…”