Interleukin-4- and -13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease

Akiho, Hirotada; Lovato, Paola; Deng, Yikang; Ceponis, Peter J. M.; Blennerhassett, Patricia; Collins, Stephen M.

doi:10.1152/ajpgi.00273.2004

Cited by 37 publications

(37 citation statements)

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“…Inflammation is associated with structural and functional changes in the contractile apparatus of gut that leads to altered motor function (6,43). Hypercontractility, especially of longitudinal smooth muscle, has been reported in IBD patients, especially Crohn's patients, and is a characteristic of a variety of models of gut inflammation (2,3,20,27,33,43,51). Similarly, hypercontractility of airway smooth muscle is also a hallmark of lung inflammation and BDNF upregulation during airway inflammation has been shown to mediate this hypercontractility (1,28,40,49,57).…”

Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Qudah

Anderson

Mahavadi

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Al-Qudah M, Anderson CD, Mahavadi S, Bradley ZL, Akbarali HI, Murthy KS, Grider JR. Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C. Am J Physiol Gastrointest Liver Physiol 306: G328 -G337, 2014. First published December 19, 2013 doi:10.1152/ajpgi.00203.2013.-Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of proteins best known for its role in neuronal survival, differentiation, migration, and synaptic plasticity in central and peripheral neurons. BDNF is also widely expressed in nonneuronal tissues including the gastrointestinal tract. The role of BDNF in intestinal smooth muscle contractility is not well defined. The aim of this study was to identify the role of BDNF in carbachol (CCh)-and substance P (SP)-induced contraction of intestinal longitudinal smooth muscle. BDNF, selective tropomyosin-related kinase B (TrkB) receptor agonists, and pharmacological inhibitors of signaling pathways were examined for their effects on contraction of rabbit intestinal longitudinal muscle strips induced by CCh and SP. BDNF activation of intracellular signaling pathways was examined by Western blot in homogenates of muscle strips and isolated muscle cells. One-hour preincubation with BDNF enhanced intestinal muscle contraction induced by CCh but not by SP. The selective synthetic TrkB agonists LM 22A4 and 7,8-dihydroxyflavone produced similar effects to BDNF. The Trk antagonist K-252a, a TrkB antibody but not p75NTR antibody, blocked the effect of BDNF. The enhancement of CCh-induced contraction by BDNF was blocked by the phospholipase C (PLC) antagonist U73122, but not by ERK1/2 or Akt antagonists. Direct measurement in muscle strips and isolated muscle cells showed that BDNF caused phosphorylation of TrkB receptors and PLC-␥, but not ERK1/2 or Akt. We conclude that exogenous BDNF augments the CCh-induced contraction of longitudinal muscle from rabbit intestine by activating TrkB receptors and subsequent PLC activation.neurotrophins; smooth muscle contraction; Trk receptors BRAIN DERIVED-NEUROTROPHIC FACTOR (BDNF) belongs to the neurotrophin family of peptides that includes nerve growth factor, neurotrophin-3, and neurotrophin-4/5. Neurotrophins are best known for their prolonged effects and role in neuronal survival, development, differentiation, migration, and synaptic plasticity (47, 56). BDNF mediates its biological functions by activating two distinct cell membrane receptors: p75NTR, a low-affinity receptor to which all neurotrophins bind, and tropomyosin-related kinase B (TrkB), a high-affinity receptor that preferentially binds BDNF (46). BDNF binding to TrkB induces autophosphorylation of the receptor intracellular tyrosine kinase domain that leads to activation of one or more of three canonical and independent intracellular signaling pathways: the Ras/extracellular signal-regulated kinase (ERK) pathway, the phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway, and the phospholipase C-␥1 (PLC-...

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Section: Discussionmentioning

confidence: 99%

Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Qudah

Anderson

Mahavadi

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Section: Motility Disorders In Intestinal Inflammationmentioning

confidence: 99%

“…These differences in contractile responses may be due to differences in cytokine profiles. Reports from the Collins group (Akiho et al, 2002;Akiho et al, 2005a;Akiho et al, 2005b) have suggested that nematode-induced hypercontractility is mediated by an increase in prostaglandin E2 (PGE2) levels after induction of the expression of Th2 cytokines such as interleukin (IL)-4 and IL-13.On the other hand, reports suggest that TNBS-induced gut inflammation is mediated mainly by Th1 cytokines such as IL-1β, tumor necrosis factor-α (TNF-α) and IL-12 (Neurath et al, 1995; Kinoshita et al, 2006; Kiyosue et al, 2006;Ohama et al, 2007b). In this review, we focused on the molecular mechanisms that are responsible for the decreased motility of the inflamed intestine.…”

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confidence: 99%

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

Ohama

Hori

Ozaki

2007

J Smooth Muscle Res

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Intestinal inflammation alters the contractile activity of intestinal smooth muscle. Motility disorders of the gastrointestinal tract are clinically important symptoms, because they are often associated with severe interstitial inflammation. In addition, the motility disorders secondarily induce abnormal growth of the intestinal flora, and the resulting disturbance of this flora aggravates the pathogenesis of mucosal inflammation. This in turn aggravates the intestinal dysmotility; i.e., it is an inflammatory spiral. Therefore, it is important to elucidate the mechanisms involved in the changes in motor function which occur in intestinal inflammation. Recent studies have revealed several molecular mechanisms responsible for the decreased motility which occurs in an inflamed gastrointestinal tract. In the present review, we discuss the functional failure of smooth muscle cells, including changes in the activity of muscarinic receptors, ion channels and the endogenous myosin phosphatase inhibitor CPI-17.Key words: intestinal inflammation, smooth muscle, contraction, CPI-17 Motility disorders in intestinal inflammationMotility disorders of the gastrointestinal tract are extremely important clinically because they can lead to systemic disease. In humans and in animal models, intestinal inflammation results in the disturbance of motility, which may reflect changes in smooth muscle function and/or the enteric nervous system (Vermillion et al., 1993;Vrees et al., 2002). Both increased and decreased smooth muscle contractility has been observed in intestinal inflammation. In a model of nematode infection-induced gut inflammation, such as Trichinella spiralis infectioninduced gut inflammation, smooth muscle contractility is increased (Vermillion and Collins, 1988;Blennerhassett et al., 1992). On the other hand, smooth muscle contractility is decreased T. OHAMA et al. 44 in the intestinal inflammation induced by trinitrobenzene sulphonic acid (TNBS), surgical manipulation, experimental obstruction, hemorrhagic shock, or peritonitis (Kalff et al., 1998;Moreels et al., 2001; Koyluoglu et al., 2002;Hierholzer et al., 2004; Kinoshita et al., 2006; Kiyosue et al., 2006;Won et al., 2006; Kinoshita et al., 2007;Ohama et al., 2007b). These differences in contractile responses may be due to differences in cytokine profiles. Reports from the Collins group (Akiho et al., 2002;Akiho et al., 2005a;Akiho et al., 2005b) have suggested that nematode-induced hypercontractility is mediated by an increase in prostaglandin E2 (PGE2) levels after induction of the expression of Th2 cytokines such as interleukin (IL)-4 and IL-13.On the other hand, reports suggest that TNBS-induced gut inflammation is mediated mainly by Th1 cytokines such as IL-1β, tumor necrosis factor-α (TNF-α) and IL-12 (Neurath et al., 1995; Kinoshita et al., 2006; Kiyosue et al., 2006;Ohama et al., 2007b). In this review, we focused on the molecular mechanisms that are responsible for the decreased motility of the inflamed intestine. Nematode-induced hyper-co...

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“…Tumor necrosis factor (TNF)-␣ can attenuate carbachol (CCh)-induced contraction in colonic inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in C57BL/6 mice (Ohama et al, 2007). Alternatively, it was reported that incubation of human cultured smooth muscle cells with T H 2 cytokines, interleukin (IL)-4 or IL-13, enhanced CCh-induced contraction via activation of signal transducer and activator of transcription 6 (STAT6) (Akiho et al, 2005b). Collectively, the T H 1 and T H 2 immune responses are associated with hypocontractility and hypercontractility of inflamed intestinal smooth muscle, respectively.…”

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confidence: 99%

Mitogen-Activated Protein Kinase Pathways Contribute to Hypercontractility and Increased Ca2+ Sensitization in Murine Experimental Colitis

Ihara

Beck

Chappellaz

et al. 2009

Molecular Pharmacology

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Inflammatory bowel disease (IBD) is associated with intestinal smooth muscle dysfunction. Many smooth muscle contractile events are associated with alterations in Ca 2ϩ -sensitizing pathways. The aim of the present study was to assess the effect of colitis on Ca 2ϩ sensitization and the signaling pathways responsible for contractile dysfunction in murine experimental colitis. Colitis was induced in BALB/c mice by providing 5% dextran sulfate sodium (DSS) in drinking water for 7 days. Contractile responses of colonic circular smooth muscle strips to 118 mM K ϩ and carbachol (CCh) were assessed. DSS induced a T H 2 colitis [increased interleukin (IL)-4 and IL-6] with no changes in T H 1 cytokines. Animals exposed to DSS had increased CCh-induced contraction (3.5-fold) and CCh-induced Ca 2ϩ -sensitization (2.2-fold) responses in intact and ␣-toxin permeabilized colonic smooth muscle, respectively. The contributions of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) to CCh-induced contractions were significantly increased during colitis. Ca 2ϩ -independent contraction induced by microcystin was potentiated (1.5-fold) in mice with colitis. ERK and p38MAPK (but not Rho-associated kinase) contributed to this potentiation. ERK1/2 and p38MAPK expression were increased in the muscularis propria of colonic tissue from both DSS-treated mice and patients with IBD (ulcerative colitis Ͼ Ͼ Crohn's disease). Murine T H 2 colitis resulted in colonic smooth muscle hypercontractility with increased Ca 2ϩ sensitization. Both ERK and p38MAPK pathways contributed to this contractile dysfunction, and expression of these molecules was altered in patients with IBD.It has been hypothesized that an imbalance of the T H 1/T H 2 immune response plays a central role in the pathogenesis of inflammatory bowel disease (IBD) (Neurath et al., 2002;Xavier and Podolsky, 2007). The mediators of intestinal inflammation are also known to impair gastrointestinal motility in human disease and animal models, which may be a reflection of altered smooth muscle function. Alterations in gastrointestinal motility with resultant changes in transit contribute to the abdominal pain, intestinal cramping, and diarrhea characteristically associated with IBD. Furthermore, defects in smooth muscle function can lead to the development of toxic megacolon. While it is commonly accepted that smooth muscle contractility is altered in inflamed intestine, there is still considerable disagreement whether intestinal contractility is increased or decreased in IBD. T H 1 and T H 2 immune responses play different roles in dysfunction of smooth muscle contractility. Tumor necrosis factor

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Interleukin-4- and -13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease

Abstract: . Interleukin-4-and -13-induced hypercontractility of human intestinal muscle cells-implication for motility changes in Crohn's disease.

Cited by 37 publications

References 56 publications

Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Brain-derived neurotrophic factor enhances cholinergic contraction of longitudinal muscle of rabbit intestine via activation of phospholipase C

Mechanism of abnormal intestinal motility in inflammatory bowel disease: how smooth muscle contraction is reduced?

Mitogen-Activated Protein Kinase Pathways Contribute to Hypercontractility and Increased Ca2+ Sensitization in Murine Experimental Colitis

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