Protective effects of cathelicidin‐encoding <i>Lactococcus lactis</i> in murine ulcerative colitis

Wong, Clover Ching Man; Zhang, Lin; Li, Zhe Jie; Wu, William Ka Kei; Ren, Shun X.; Chen, Yangchao; Ng, Tzi Bun; Cho, Chi Hin

doi:10.1111/j.1440-1746.2012.07158.x

Cited by 54 publications

(39 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the role of LL‐37 in immune‐mediated chronic inflammation remains largely unresolved. Recent studies have suggested that cathelicidins may be protective in certain immune‐mediated inflammatory diseases . Consistent with this, in a recent study we demonstrated that an LL‐37‐derived peptide IG‐19 can indeed alleviate the disease process in a murine model of inflammatory arthritis .…”

Section: Introductionsupporting

confidence: 87%

Human cathelicidin LL‐37 and its derivative IG‐19 regulate interleukin‐32‐induced inflammation

Choi

Napper²,

Mookherjee

2014

Immunology

View full text Add to dashboard Cite

SummaryHuman cathelicidin LL-37 protects against infections and endotoxininduced inflammation. In a recent study we have shown that IG-19, an LL-37-derived peptide, protects in a murine model of arthritis. Cytokine interleukin-32 (IL-32) is elevated and directly associated with the disease severity of inflammatory arthritis. Therefore, in this study we examined the effects of LL-37 and IG-19 on IL-32-induced responses in human peripheral blood-derived mononuclear cells (PBMC) and macrophages. We showed that CD14 + monocytes are the primary cells that produce pro-inflammatory tumour necrosis factor-a (TNF-a) following stimulation of PBMC with IL-32. We demonstrated that LL-37 and IG-19 significantly suppress IL-32-induced production of pro-inflammatory cytokines, e.g. TNF-a and IL-1b, without altering chemokine production. In contrast, LL-37 and IG-19 enhance the production of the anti-inflammatory cytokine IL-1RA. Further mechanistic studies revealed that LL-37 and IG-19 suppress IL-32-mediated phosphorylation of Fyn (Y420) Src kinase. In contrast, IL-32-mediated phosphorylation of AKT-1 (T308) and MKP-1 (S359) is not suppressed by the peptides. LL-37 and IG-19 alone induce the phosphorylation of MKP-1 (S359), which is a known negative regulator of inflammation. Furthermore, the peptides induce the activity of p44/ 42 mitogen-activated protein kinase, which is known to phosphorylate MKP-1 (S359). This is the first study to demonstrate the regulation of IL-32-induced inflammation by LL-37 and its derivative peptide IG-19. The mechanistic results from this study suggest that regulation of immunemediated inflammation by these peptides may be controlled by the dual phosphatase MKP-1. We speculate that LL-37 and its derivatives may contribute to the control of immune-mediated inflammatory diseases.

show abstract

Section: Introductionsupporting

confidence: 87%

Human cathelicidin LL‐37 and its derivative IG‐19 regulate interleukin‐32‐induced inflammation

Choi

Napper²,

Mookherjee

2014

Immunology

View full text Add to dashboard Cite

show abstract

“…A previous study demonstrated that the intrarectal administration of mouse cathelin-related antimicrobial peptide (mCRAMP) alleviates DSS-induced colitis by preserving the mucus layer and reducing pro-inflammatory cytokines production [45]. A mutant of Lactococcus lactis NZ3900 that produces mCRAMP was tested in a murine model of DSS-induced colitis for seven days.…”

Section: Resultsmentioning

confidence: 99%

“…The number of apoptotic cells, myeloperoxidase (MPO) activity, and malondialdehyde level were also significantly reduced. The increases in fecal microbiota in colitis animals were markedly prevented [45]. …”

Section: Resultsmentioning

confidence: 99%

Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases

et al. 2017

View full text Add to dashboard Cite

Probiotics and synbiotics are used to treat chronic diseases, principally due to their role in immune system modulation and the anti-inflammatory response. The present study reviewed the effects of probiotics and synbiotics on intestinal chronic diseases in in vitro, animal, and human studies, particularly in randomized clinical trials. The selected probiotics exhibit in vitro anti-inflammatory properties. Probiotic strains and cell-free supernatants reduced the expression of pro-inflammatory cytokines via action that is principally mediated by toll-like receptors. Probiotic administration improved the clinical symptoms, histological alterations, and mucus production in most of the evaluated animal studies, but some results suggest that caution should be taken when administering these agents in the relapse stages of IBD. In addition, no effects on chronic enteropathies were reported. Probiotic supplementation appears to be potentially well tolerated, effective, and safe in patients with IBD, in both CD and UC. Indeed, probiotics such as Bifidobacterium longum 536 improved the clinical symptoms in patients with mild to moderate active UC. Although it has been proposed that probiotics can provide benefits in certain conditions, the risks and benefits should be carefully assessed before initiating any therapy in patients with IBD. For this reason, further studies are required to understand the precise mechanism by which probiotics and synbiotics affect these diseases.

show abstract

“…The authors observed a reduced number of bacteria in the feces from animals that received the L. lactis -cathelicidin strain, suggesting an anti-microbial effect of the strain. According to the study, these findings were correlated to reduced tissue damage and MPO activity (Wong et al, 2012). …”

Section: The Use Of Recombinant Lactic Acid Bacteria For the Treatmenmentioning

confidence: 97%

Use of Wild Type or Recombinant Lactic Acid Bacteria as an Alternative Treatment for Gastrointestinal Inflammatory Diseases: A Focus on Inflammatory Bowel Diseases and Mucositis

et al. 2017

View full text Add to dashboard Cite

The human gastrointestinal tract (GIT) is highly colonized by bacterial communities, which live in a symbiotic relationship with the host in normal conditions. It has been shown that a dysfunctional interaction between the intestinal microbiota and the host immune system, known as dysbiosis, is a very important factor responsible for the development of different inflammatory conditions of the GIT, such as the idiopathic inflammatory bowel diseases (IBD), a complex and multifactorial disorder of the GIT. Dysbiosis has also been implicated in the pathogenesis of other GIT inflammatory diseases such as mucositis usually caused as an adverse effect of chemotherapy. As both diseases have become a great clinical problem, many research groups have been focusing on developing new strategies for the treatment of IBD and mucositis. In this review, we show that lactic acid bacteria (LAB) have been capable in preventing and treating both disorders in animal models, suggesting they may be ready for clinical trials. In addition, we present the most current studies on the use of wild type or genetically engineered LAB strains designed to express anti-inflammatory proteins as a promising strategy in the treatment of IBD and mucositis.

show abstract

Protective effects of cathelicidin‐encoding Lactococcus lactis in murine ulcerative colitis

Abstract: mCRAMP-transformed L. lactis has been shown to produce mCRAMP, effectively preventing murine UC. Oral administration of this biological preparation is better than sulfasalazine for the treatment of UC.

Cited by 54 publications

References 44 publications

Human cathelicidin LL‐37 and its derivative IG‐19 regulate interleukin‐32‐induced inflammation

Human cathelicidin LL‐37 and its derivative IG‐19 regulate interleukin‐32‐induced inflammation

Evidence of the Anti-Inflammatory Effects of Probiotics and Synbiotics in Intestinal Chronic Diseases

Use of Wild Type or Recombinant Lactic Acid Bacteria as an Alternative Treatment for Gastrointestinal Inflammatory Diseases: A Focus on Inflammatory Bowel Diseases and Mucositis

Contact Info

Product

Resources

About