Functional Expression of the Interleukin-11 Receptor α-Chain and Evidence of Antiapoptotic Effects in Human Colonic Epithelial Cells

Kiessling, Stefan G.; Müller‐Newen, Gerhard; Leeb, Sandra N.; Hausmann, Martin; Rath, Heiko C.; Sträter, Jörn; Spöttl, T.; Schlottmann, Klaus; Grossmann, Johannes; Montero‐Julian, Félix A.; Schölmerich, Jürgen; Andus, Tilo; Buschauer, Armin; Heinrich, Peter C.; Rogler, Gerhard

doi:10.1074/jbc.m312757200

Cited by 62 publications

(34 citation statements)

References 57 publications

(60 reference statements)

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“…However, as the receptors of these cytokines and growth factors are present on both innate and acquired cells, activation of STAT3 is likely to occur in both cell types [5,14,[34][35][36]57,58] . Therefore, as the function of STAT3 is a double-edged sword, careful attention should be directed toward the cell population that is being targeted when one contemplates STAT3 inhibition or activation in human IBD [59] .…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, GH and IL-11, both of which activate STAT3 predominantly in CECs, contribute to the suppression of experimental colitis [33][34][35] . Of note, human trials utilizing GH, IL-11 and anti-IL-6R mAb have been conducted and have shown that the strategies using these products are beneficial to IBD patients [38][39][40] (Figure 1).…”

Section: The Role Of Stat3-activators On Ibdmentioning

confidence: 99%

“…Among these, roles of IL-6, IL-11, IL-15, HGF, GH and leptin in experimental colitis have been demon strated [9][10][11][12][33][34][35][36] . For example, IL-6, IL-15 and leptin play a pathogenic role in colitis by activating STAT3 predominantly in the acquired immune cells [9,10,12,36,37] (Figure 1).…”

Section: The Role Of Stat3-activators On Ibdmentioning

confidence: 99%

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Role of STAT3 in inflammatory bowel disease

Sugimoto¹

2008

WJG

111

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Signal transducers and activators of transcription 3 (STAT3) play an important role in various autoimmune disorders including inflammatory bowel disease (IBD). Recent studies have revealed that STAT3 activation plays distinctly different roles between innate immune responses and acquired immune responses in colitis. STAT3-mediated activation of acquired immune responses plays a pathogenic role in colitis by enhancing the survival of pathogenic T cells. In contrast, STAT3-mediated activation of innate responses contributes to the suppression of colitis. This review will summarize the current understanding of the roles of STAT3 in IBD and the potential of targeting STAT3 for the treatment of IBD, emphasizing recent observations.

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Section: Resultsmentioning

confidence: 99%

Section: The Role Of Stat3-activators On Ibdmentioning

confidence: 99%

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Role of STAT3 in inflammatory bowel disease

Sugimoto¹

2008

WJG

111

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“…The underlying mechanism is considered to relate to the dampening effects of IL-11 on the inflammatory response by reducing macrophage cytokine and reactive oxygen species production (Redlich et al 1996;Trepicchio et al 1996;Waxman et al 1998Waxman et al , 2003Zheng et al 2001). Moreover, IL-11 was recently shown to mediate direct antiapoptotic effects on human colonic epithelial cells (Kiessling et al 2004). IL-11 also prevents cartilage matrix degradation in chronically inflamed joints by inducing the expression of tissue inhibitor of metalloproteinases (TIMP) (Maier et al 1993) and is an important regulator of bone remodeling (Elias et al 1995;Takeuchi et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Multiple and highly divergent IL-11 genes in teleost fish

et al. 2005

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Interleukin-11 (IL-11) is a key cytokine in the regulation of proliferation and differentiation of hematopoietic progenitors and is also involved in bone formation, adipogenesis, and protection of mucosal epithelia. Despite this prominent role in diverse physiological processes, IL-11 has been described in only four mammalian species, and recently, in rainbow trout (Oncorhynchus mykiss). Here we report the presence of IL-11 in common carp (Cyprinus carpio), a bony fish species related to zebrafish. IL-11 is expressed in most carp organs and tissues. In vitro expression of IL-11 in cultured macrophages is enhanced by stimulation with lipopolysaccharide and is markedly inhibited by cortisol. A detailed and systematic scan of several fish genome databases confirms that IL-11 is present in all fish, but also reveals the presence of a second, substantially different IL-11 gene in the genomes of phylogenetically distant fish species. We designated both fish paralogues IL-11a and IL-11b. Although sequence identity between fish IL-11a and IL-11b peptides is low, the conservation of their gene structures supplemented by phylogenetic analyses clearly illustrate the orthology of both IL-11a and IL-11b genes of fish with mammalian IL-11. The presence of IL-11 genes in fish demonstrates its importance throughout vertebrate evolution, although the presence of duplicate and divergent IL-11 genes differs from the single IL-11 gene that exists in mammals.

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“…Binding of IL-11 to IL11RA triggers heterodimerization, tyrosine phosphorylation, and activation of gp130 (Fourcin et al, 1994). The activated IL11RA -gp130 receptor complex further activates Jak family of tyrosine kinases, JAK1, JAK2, and TYK2 (Bao et al, 2006;Kiessling et al, 2004;Berger et al, 1994). JAK2 catalyzes the phosphorylation and nuclear translocation of STAT3 and STAT1 (Idris et al, 2012;Tenney et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

IL-11/IL11RA receptor mediated signaling: a web accessible knowledgebase

Balakrishnan

Soman

Patil

et al. 2013

Cell Communication & Adhesion

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Interleukin-11 (IL-11) is a pleiotropic cytokine that belongs to gp130 family. It plays a signifi cant role in the synthesis and maturation of hematopoietic cells, inhibition of adipogenesis, regulation of embryo implantation, and trophoblasts invasion. Although IL-11 signaling has been described in several biological processes, a centralized resource documenting these molecular reactions induced by IL-11 is not publicly available. In the current study, we have manually annotated the molecular reactions and interactions induced by IL-11 from literature available. We have documented 40 unique molecules involved in 18 protein -protein interactions, 26 enzyme -substrate reactions, 7 translocation events, and 4 activation/ inhibition reactions. We have also annotated 23 genes reported to be differentially regulated under IL-11 stimulation. We have enabled the data availability in standard exchange formats from ' NetPath ' , a repository for signaling pathways. We believe that this will help in the identifi cation of potential therapeutic targets in IL-11-associated disorders.

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Functional Expression of the Interleukin-11 Receptor α-Chain and Evidence of Antiapoptotic Effects in Human Colonic Epithelial Cells

Cited by 62 publications

References 57 publications

Role of STAT3 in inflammatory bowel disease

Role of STAT3 in inflammatory bowel disease

Multiple and highly divergent IL-11 genes in teleost fish

IL-11/IL11RA receptor mediated signaling: a web accessible knowledgebase

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