CXCL8 chemokine in ulcerative colitis

Zhu, Yuemin; Yang, Shun Tai; Zhao, Nan; Liu, Chuanguo; Zhang, Fayan; Guo, Yuting; Liu, Huimin

doi:10.1016/j.biopha.2021.111427

Cited by 55 publications

(36 citation statements)

References 105 publications

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“…Inflammatory bowel diseases (IBDs) are disorders characterized by the chronic abnormal inflammation of the gastrointestinal tract, which triggers an uncontrolled and deleterious inflammatory response 1 , 2 during which levels of interleukine-8 (IL-8) cytokines increase 3 , 4 and reactive oxygen species (ROS) are overproduced 5 . The two main types of IBDs are Crohn's disease (CD) and ulcerative colitis (UC) 6 , which each display distinct physiological symptoms.…”

Section: Introductionmentioning

confidence: 99%

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

Kropp

Corf²,

Relizani³

et al. 2021

Sci Rep

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Christensenellaceae is a family of subdominant commensal bacteria found in humans. It is thought to play an important role in gut health by maintaining microbial symbiosis. Indeed, these bacteria occur at significantly lower levels or are absent in individuals suffering from inflammatory bowel diseases (IBDs). Here, we explored if type species Christensenella minuta (strain: DSM 22607) could have the potential to help treat IBDs. We assessed key properties displayed by the bacterium using a combination of in vitro and in vivo assays. We found that while C. minuta is a strict anaerobe, it is also oxygen tolerant. Additionally, we observed that the species produces high levels of acetate and moderate levels of butyrate. We performed deep phenotyping using Biolog microarrays. Using human intestinal cell lines, we discovered that C. minuta demonstrated strong anti-inflammatory activity, resulting in reduced levels of proinflammatory IL-8 cytokines via the inhibition of the NF-κB signaling pathway. Furthermore, C. minuta protected intestinal epithelial integrity in vitro. Finally, in two distinct animal models of acute colitis, C. minuta prevented intestinal damage, reduced colonic inflammation, and promoted mucosal healing. Together, these results indicate that C. minuta has potent immunomodulatory properties, underscoring its potential use in innovative microbiome-based IBD biotherapies.

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Section: Introductionmentioning

confidence: 99%

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

Kropp

Corf²,

Relizani³

et al. 2021

Sci Rep

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show abstract

“…CXCL8 , encoding the neutrophil chemoattractant IL-8, was also upregulated in the patient’s M1 and M2 macrophages. Aberrant regulation of IL-8 has been implicated in numerous inflammatory diseases [ 50 – 53 ], including mucosal tissues, which may partly explain the mucosal ulceration observed here.…”

Section: Discussionmentioning

confidence: 82%

An Atypical Autoinflammatory Disease Due to an LRR Domain NLRP3 Mutation Enhancing Binding to NEK7

et al. 2021

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The NLRP3 inflammasome is a vital mediator of innate immune responses. There are numerous NLRP3 mutations that cause NLRP3-associated autoinflammatory diseases (NLRP3-AIDs), mostly in or around the NACHT domain. Here, we present a patient with a rare leucine-rich repeat (LRR) domain mutation, p.Arg920Gln (p.R920Q), associated with an atypical NLRP3-AID with recurrent episodes of sore throat and extensive oropharyngeal ulceration. Unlike previously reported patients, who responded well to anakinra, her oral ulcers did not significantly improve until the PDE4 inhibitor, apremilast, was added to her treatment regimen. Here, we show that this mutation enhances interactions between NLRP3 and its endogenous inhibitor, NIMA-related kinase 7 (NEK7), by affecting charge complementarity between the two proteins. We also demonstrate that additional inflammatory mediators, including the NF-кB and IL-17 signalling pathways and IL-8 chemokine, are upregulated in the patient’s macrophages and may be directly involved in disease pathogenesis. These results highlight the role of the NLRP3 LRR domain in NLRP3-AIDs and demonstrate that the p.R920Q mutation can cause diverse phenotypes between families.

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“…It was previously shown that CCL2 recruits macrophages to sites of inflammation after allergen exposure [ 32 ], and that the blocking of CCL2 signaling pathway prevents Th2 inflammatory response in allergic asthma [ 33 ]. TNF-α and CXCL8 were reported to serve as important inflammatory cytokines by attracting neutrophils and basophils and promoting inflammatory reactions, not only in relation to allergies [ 34 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3

Bilotta

Paruchuru

Feilhauer

et al. 2021

IJMS

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Mast cells play a critical role as main effector cells in allergic and other inflammatory diseases. Usage of anti-inflammatory nutraceuticals could be of interest for affected patients. Resveratrol, a natural polyphenol found in red grapes, is known for its positive properties. Here, we analyzed the effects of resveratrol on FcεRI-mediated activation of mature human mast cells isolated from intestinal tissue (hiMC). Resveratrol inhibited degranulation and expression of cytokines and chemokines such as CXCL8, CCL2, CCL3, CCL4, and TNF-α in a dose-dependent manner. Further, resveratrol inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription (STAT) 3. ERK1/2 is known to be involved in cytokine expression of hiMC and to directly interact with STAT3. Mitochondrial STAT3 is phosphorylated by ERK1/2 and contributes to mast cell degranulation. We were able to isolate mitochondrial fractions from small hiMC numbers and could show that activation of mitochondrial STAT3 and ERK1/2 in hiMC was also inhibited by resveratrol. Our results indicate that resveratrol inhibits hiMC activation by inhibiting the phosphorylation of mitochondrial and nuclear ERK1/2 and STAT3, and it could be considered as an anti-inflammatory nutraceutical in the treatment of mast cell-associated diseases.

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CXCL8 chemokine in ulcerative colitis

Cited by 55 publications

References 105 publications

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

The Keystone commensal bacterium Christensenella minuta DSM 22607 displays anti-inflammatory properties both in vitro and in vivo

An Atypical Autoinflammatory Disease Due to an LRR Domain NLRP3 Mutation Enhancing Binding to NEK7

Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3

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