Synthesis of immune modulators by smooth muscles

Abstract

The primary function of smooth muscle cells is to contract and alter the stiffness or diameter of hollow organs such as blood vessels, the airways and the gastrointestinal and urogenital tracts. In addition to purely structural functions, smooth muscle cells may play important metabolic roles, particularly in various inflammatory responses. In cell culture, these cells have been shown to be metabolically dynamic, synthesizing and secreting extracellular matrix proteins, glycosaminoglycans and a wide variety of cell-cell signaling proteins, such as interleukins, chemokines and peptide growth factors. Secreted cell signaling proteins participate in the inflammatory response of smooth muscle-containing organs, and some can also stimulate smooth muscle migration, proliferation and contraction. The cellular signaling pathways controlling synthesis of these signaling proteins are similar to those used by cells mediating innate immunity and may contribute to pathogenesis of diverse diseases including atherosclerosis, asthma, inflammatory bowel diseases and preterm labor. Appreciating the role of smooth muscle cells in these diseases may lead to better understanding of the beneficial effects of anti-inflammatory drugs as well as identification of new targets for anti-inflammatory therapy.

Mechanisms of Vascular Smooth Muscle Cell Migration

“…29 This is only one example of the well-documented ability of growth factors and cytokines to stimulate their own synthesis by smooth muscles, as well as synthesis of other growth factors and cytokines. 30,31 Therefore, both direct and indirect effects of signaling proteins on VSM migration are very likely to occur in vivo during a response to injury or inflammation.…”

Cytokine-Induced S-Nitrosylation of Soluble Guanylyl Cyclase and Expression of Phosphodiesterase 1A Contribute to Dysfunction of Longitudinal Smooth Muscle Relaxation

“…activity of various signaling molecules that regulate smooth muscle contraction and relaxation (Akiho et al, 2002;Shi et al, 2003;Cao et al, 2004;Jin et al, 2004;Salinthone et al, 2004;Singer et al, 2004;Shi and Sarna, 2005;Zhao et al, 2005Zhao et al, , 2006Khan and Collins, 2006;Ohama et al, 2007;Ihara et al, 2012;Shea-Donohue et al, 2012;Yang et al, 2013). Previous studies have identified that signaling pathways that mediate initial and sustained contraction in intestinal longitudinal muscle are distinct from those in circular muscle (Grider and Makhlouf, 1988;Murthy, 2006).…”

Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation

“…Two important components of the pathway, namely the RhoGEF, LARG, and the MLCP activator, telokin, were shown to be targets of proinflammatory cytokines, and changes in their expression underlay the hypercontractile response of intestinal longitudinal smooth muscle during inflammation. Smooth muscle cells act as both source and target of pro-and anti-inflammatory mediators including cytokines, chemokines, and growth factors (47,51,54). Earlier studies on TNBS-induced colitis have shown that IL-1␤ and TNF-␣ induce a variety of nuclear factors (e.g., NF-B) and kinases, including ERK1/2, p38 MAP kinase, Jun kinase, and PI 3-kinase (5, 18, 24, 49 -51).…”