Non-core Region Modulates Interleukin-11 Signaling Activity

Yanaka, Saeko; Sano, Emiko; Naruse, Norio; Miura, Koryo; Futatsumori-Sugai, Mutsumi; Caaveiro, José M. M.; Tsumoto, Kouhei

doi:10.1074/jbc.m110.152561

Cited by 13 publications

(6 citation statements)

References 55 publications

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“…IL-11R agonist is a modified version of human IL-11, where the mutations were introduced into the linker region of human IL-11 to increase stability and biological activities to 10 fold higher than the original IL-11. The detailed characterization was described elsewhere 48 . Mice were sacrificed at 3 h after injection.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

et al. 2021

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Interleukin (IL)-11 is a member of the IL-6 family of cytokines and is involved in multiple cellular responses, including tumor development. However, the origin and functions of IL-11-producing (IL-11+) cells are not fully understood. To characterize IL-11+ cells in vivo, we generate Il11 reporter mice. IL-11+ cells appear in the colon in murine tumor and acute colitis models. Il11ra1 or Il11 deletion attenuates the development of colitis-associated colorectal cancer. IL-11+ cells express fibroblast markers and genes associated with cell proliferation and tissue repair. IL-11 induces the activation of colonic fibroblasts and epithelial cells through phosphorylation of STAT3. Human cancer database analysis reveals that the expression of genes enriched in IL-11+ fibroblasts is elevated in human colorectal cancer and correlated with reduced recurrence-free survival. IL-11+ fibroblasts activate both tumor cells and fibroblasts via secretion of IL-11, thereby constituting a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment.

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Section: Methodsmentioning

confidence: 99%

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

et al. 2021

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“…Thus, we tested whether IL-11 indeed protected hepatocytes from APAP-induced liver injury. To do this, we generated a super agonist of the human IL-11 receptor (IL-11R), designated N T -3N, in which we introduced three N-glycosylation sites into the noncore region of human IL-11 (25). We found that in vivo injection of mice with N T -3N induced the phosphorylation of STAT3 and the increased expression of its target genes, including Bcl2l1 and Myc (fig.…”

Section: An Il-11 Receptor Agonist Ameliorates Apap-induced Liver Inj...mentioning

confidence: 99%

“…Characterization and production of the human IL-11R agonist N T -3N was described previously (25). While searching for a super agonist of IL-11R by introducing N-glycosylation sites in the noncore regions of IL-11, we found that a mutant, designated N T -3N, in which nine amino acid residues (NASNASNAS) were introduced between Pro 22 and Gly 23 of IL-11, exhibited a 10-fold higher affinity for human IL-11R than is exhibited by wild-type IL-11 and a 10-fold higher cell proliferation activity (25). (The superscript numbers indicate amino acid positions from the N terminus of human IL-11.)…”

Section: Production Of the Il-11r Agonist N T -3nmentioning

confidence: 99%

Interleukin-11 Links Oxidative Stress and Compensatory Proliferation

et al. 2012

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Apoptotic cells can stimulate the compensatory proliferation of surrounding cells to maintain tissue homeostasis. Although oxidative stress is associated with apoptosis and necrosis, whether it contributes to compensatory proliferation is unknown. Here, we showed that interleukin-11 (IL-11), a member of the IL-6 family of proinflammatory cytokines, was produced by cells in an oxidative stress-dependent manner. IL-11 production depended on the activation in dying cells of extracellular signal-regulated kinase 2, which in turn caused the phosphorylation and accumulation of the transcription factor Fra-1 by preventing its proteasome-dependent degradation. Fra-1 was subsequently recruited to the Il11 promoter and activated gene transcription. Upon acute liver injury in mice, IL-11 was mainly produced by hepatocytes in response to reactive oxygen species that were presumably released from dying hepatocytes. IL-11 that was secreted by the dying cells then induced the phosphorylation of the transcription factor STAT3 in adjacent healthy hepatocytes, which resulted in their compensatory proliferation. Furthermore, an IL-11 receptor (IL-11R) agonist enhanced the proliferation of hepatocytes and ameliorated oxidative stress upon acetaminophen-induced liver injury. Conversely, the effects of acetaminophen were exacerbated in mice deficient in the IL-11R α subunit. Together, these results suggest that IL-11 provides a functional link between oxidative stress and compensatory proliferation.

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“…Arginine-specific mono ADP-ribosylation in vitro of antimicrobial peptides by ADPribosylating toxins (Castagnini et al, 2012) Interleukin-5 receptor TOF Mutation of N-glycosylation sites to determine effect on function (Ishino et al, 2011) Interleukin-11 TOF (sinapinic), glycoprotein Introduction of O-glycans in the non-core region to investigate function (Yanaka et al, 2011) Lipoproteins…”

Section: Abbreviationsmentioning

confidence: 99%

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

Harvey

2015

Mass Spectrometry Reviews

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This review is the seventh update of the original article published in 1999 on the application of MALDI mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2012. General aspects such as theory of the MALDI process, matrices, derivatization, MALDI imaging, and fragmentation are covered in the first part of the review and applications to various structural types constitute the remainder. The main groups of compound are oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Much of this material is presented in tabular form. Also discussed are medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:255-422, 2017.

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Non-core Region Modulates Interleukin-11 Signaling Activity

Cited by 13 publications

References 55 publications

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

Interleukin-11-expressing fibroblasts have a unique gene signature correlated with poor prognosis of colorectal cancer

Interleukin-11 Links Oxidative Stress and Compensatory Proliferation

Analysis of carbohydrates and glycoconjugates by matrix‐assisted laser desorption/ionization mass spectrometry: An update for 2011–2012

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