718: Inflammatory response by uterine smooth muscle cells stimulated with IL-1b and TNFa

Abstract Objective The aim of this study was to determine if mesenchymal stem cells (MSCs) would suppress the inflammatory response in human uterine cells in an in vitro lipopolysaccharide (LPS)-based preterm birth (PTB) model. Study Design Cocultures of human uterine smooth muscle cells (HUtSMCs) and MSCs were exposed to 5 μg/mL LPS for 4 hours and further challenged with 1 μg/mL LPS for a subsequent 24 hours. Key elements of the parturition cascade regulated by toll-like receptors (TLRs) through activation of mitogen-activated protein kinases (MAPKs) were quantified in culture supernatant as biomarkers of MSC modulation. Results Coculture with MSCs significantly attenuated TLR-4, p-JNK, and p- extracellular signal-regulated kinase 1/2 (ERK1/2) protein levels compared with HUtSMCs monoculture (p = 0.05). In addition, coculture was associated with significant inhibition of proinflammatory cytokines interleukin (IL)-6 and IL-8 (p = 0.0001) and increased production of anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β1 (p = 0.0001). Conclusion MSCs appear to play a role in significantly attenuating LPS-mediated inflammation via alteration of down-stream MAPKs. MSCs may represent a novel, cell-based therapy in women with increased risk of inflammatory-mediated preterm birth.

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

Reproduction ◽

10.1530/rep-07-0289 ◽

2007 ◽

Vol 134 (6) ◽

pp. 811-822 ◽

Cited By ~ 34

Author(s):

Grégory Chevillard ◽

Anna Derjuga ◽

Dominic Devost ◽

Hans H Zingg ◽

Volker Blank

Keyword(s):

Smooth Muscle ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Muscle Cell ◽

Molecular Mechanisms ◽

Muscle Cells ◽

Interleukin 1Β ◽

Mrna Levels ◽

Uterine Smooth Muscle

We analyzed the response of uterine smooth muscle cells to interleukin-1β (IL-1β). 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-1β. In total, we identified 198 known genes whose mRNA levels are significantly modulated (> 2.0-fold change) following IL-1β exposure. We confirmed the expression changes for selected genes by independent mRNA and protein analysis. The group of genes induced by IL-1β includes transcription factors and inflammatory response genes such as nuclear factor of κ light polypeptide gene enhancer in B-cells (NFκB), pentraxin-related gene (PTX3), and tumor necrosis factor α-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-1β 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.

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Sorghum Fermented by Aspergillus oryzae NK Enhances Inhibition of Vascular Inflammation in TNF-α-stimulated Human Aortic Smooth Muscle Cells

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000496 ◽

2018 ◽

Vol 88 (5-6) ◽

pp. 309-318

Author(s):

Hae Seong Song ◽

Jung-Eun Kwon ◽

Hyun Jin Baek ◽

Chang Won Kim ◽

Hyelin Jeon ◽

...

Keyword(s):

Smooth Muscle ◽

Inflammatory Response ◽

Smooth Muscle Cells ◽

Adhesion Molecule ◽

Vascular Inflammation ◽

Muscle Cells ◽

Aortic Smooth Muscle Cells ◽

Aortic Smooth Muscle ◽

Tnf Α ◽

Cox 2

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.

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