Mitogen activated protein kinases: a role in inflammatory bowel disease?

Broom, Oliver; Widjaya, Budiman; Troelsen, Jesper T.; Olsen, Jørgen; Nielsen, Ole Haagen

doi:10.1111/j.1365-2249.2009.04033.x

Cited by 156 publications

(118 citation statements)

References 78 publications

(127 reference statements)

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“…P38 MAPK pathway regulates inflammation through downstream proteins and kinases, affecting gene transcription directly and indirectly. 37 Activated p38 MAPK increases the recruitment and activation of lymphocytes and neutrophils and delays apoptosis of these cells, 9,38,39 which are the major source of perpetual production of inflammatory mediators. In the colon of mice with DSS-induced colitis, we found a high P38/Mk2 inhibition and WIN55 effect YY Li et al expression of both p38 MAPK and its phosphorylated form p-p38 in recruited inflammatory cells of the colonic submucosal plexus, together with the predicted effects: high expression and high levels of CINC-1/KC and MCP-1 and proinflammatory cytokines both in the local tissues and in the blood.…”

Section: Mk2 Deficiency and Win55 Administration Decrease Lung Mpo Acmentioning

confidence: 99%

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis

Yuece

Cao

et al. 2013

Laboratory Investigation

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P38/Mk2 (mitogen-activated protein kinase (MAPK)-activated protein kinase-2, also known as MAKAP kinase-2) is a member of the mitogen-activated protein kinases (MAPKs) family, and participates in inflammatory responses directly or indirectly. WIN55, 212-2 (WIN55) is a synthetic non-selective agonist of cannabinoid (CB) receptors with remarkable antiinflammatory properties. This study was to explore the roles of WIN55 and p38/Mk2 signaling pathway in dextran sodium sulfate (DSS)-induced mouse colitis and ascertain their anti-inflammatory mechanisms. Colitis was induced in C57BL Mk2 gene homozygous deletion (Mk2 À / À ) and wild-type mice by replacing the drinking water with 4% DSS solution for 7 days. DSS-treated mice developed bloody stool, weight loss, and eye-visible multiple bleeding ulcers on colon mucosa. The mRNA expressions levels of TNF-a and IL-6, as well as the protein levels of p38 and its phosphorylated form (p-p38), were upregulated in the colon. The plasma levels of TNF-a, IL-6, cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), and lung myeloperoxidase (MPO) activities were raised; however, all these changes were less severe in Mk2 À / À mice. After WIN55 intervention, the Mk2 À / À mice recovered faster and better from the induced colitis than their wild-type counterparts. The results indicate that the Mk2 homozygous deletion in mice impedes the induction of experimental colitis by DSS, confirming the notion that p38/Mk2 is involved in this inflammatory response. WIN55 protects mice against DSS-induced colitis, in particular when the p38/Mk2 pathway is obstructed, implying that the activation of CB system, together with blocking of p38/Mk2 pathway, serves as a potential drug target for colitis treatment.

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Section: Mk2 Deficiency and Win55 Administration Decrease Lung Mpo Acmentioning

confidence: 99%

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis

Yuece

Cao

et al. 2013

Laboratory Investigation

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“…Moreover, MAPK including p38, JNK, and ERK1/2 are significantly activated in IBD (13)(14)(15)18). Thus we investigated whether J11-Cl can modulate the activity of MAPKs and NF-B.…”

Section: Modulation Of Pro-inflammatory Signalingmentioning

confidence: 99%

“…Several studies have reported enhanced expression and phosphorylation of MAPKs in the intestine of IBD patients, suggesting that MAPK inhibitors can be used as anti-inflammatory drugs in this disease (13)(14)(15). Activation of the NF-B pathway plays a crucial role in inflammation by inducing transcription of proinflammatory genes (16,17).…”

mentioning

confidence: 99%

A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

Choo

Lee

Yan

et al. 2015

Journal of Biological Chemistry

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Background: A newly synthesized 2-hydroxyethyl 5-chloro-4,5-didehydrojasmonate (J11-Cl) has anti-inflammatory effects in carrageenan-induced paw edema. Results: J11-Cl ameliorates colitis through activation of PPAR␥ and modulation of NF-B and MAPK signaling. Conclusion: J11-Cl acts as an effective anti-inflammatory agent. Significance: A PPAR␥ agonist is a novel candidate to treat inflammatory bowel disease.

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“…This results in the translocation of NF-κB from the cytoplasm to the nucleus to promote the expression of various proinflammatory genes, including iNOS, COX-2, and cytokines (Lan et al 2012;Hayden and Ghosh 2014). The MAPKs, such as extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAPK, are signaling molecules that also play important roles in relaying inflammatory information from the extracellular space to the cytoplasm and nucleus to modulate inflammatory responses (Broom et al 2009;Patterson et al 2014). The activation of MAPKs by phosphorylation is a critical step in the production of proinflammatory molecules in activated macrophages.…”

Section: Introductionmentioning

confidence: 99%

Fructus sophorae attenuates secretion of proinflammatory mediators and cytokines through the modulation of NF-κB and MAPK signaling pathways in LPS-stimulated RAW 264.7 macrophages

Choi

Kang²

2016

gpb

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Abstract. This study investigated the inhibitory effects and underlying mechanisms of Fructus sophorae, the dried ripe fruit of Styphnolobium japonicum (L.) Schott, on the production of proinflammatory molecules in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The results indicated that pretreatment with noncytotoxic concentrations of Fructus sophorae extract (FSE) significantly inhibited the release of the proinflammatory mediators nitric oxide (NO) and prostaglandin E 2 , which were associated with the downregulation of both mRNA and protein for inducible NO synthase and cyclooxygenase-2, respectively, in LPS-challenged RAW 264.7 cells. FSE also blocked the LPS-induced expression of the proinflammatory cytokines interleukin (IL)-6 and IL-1β. Furthermore, the results showed that FSE efficiently attenuated the LPS-induced nuclear translocation of nuclear factor-kappa B (NF-κB) and phosphorylation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) but not p38 MAPK. These results suggest that FSE exhibits anti-inflammatory activity by inhibiting proinflammatory mediators and cytokines through the inactivation of NF-κB, ERK and JNK, and it may offer therapeutic potential for treating inflammatory diseases accompanied with macrophage activation.

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Mitogen activated protein kinases: a role in inflammatory bowel disease?

Cited by 156 publications

References 78 publications

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis

Inhibition of p38/Mk2 signaling pathway improves the anti-inflammatory effect of WIN55 on mouse experimental colitis

A Novel Peroxisome Proliferator-activated Receptor (PPAR)γ Agonist 2-Hydroxyethyl 5-chloro-4,5-didehydrojasmonate Exerts Anti-Inflammatory Effects in Colitis

Fructus sophorae attenuates secretion of proinflammatory mediators and cytokines through the modulation of NF-κB and MAPK signaling pathways in LPS-stimulated RAW 264.7 macrophages

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