Næmni fyrir sýkingum og náttúrulegt ónæmi - verkefni lokið

Fréttatilkynning verkefnisstjóra

21.2.2017

Effectors of innate immunity are essential components of epithelial barrier keeping pathogens at bay but define the niche for the natural flora. Among these effectors are antimicrobial peptides (AMPs). AMPs are included in the first line of defense against infecting microbes. During bacterial infection host immunity is compromised but down regulation of host antimicrobial peptides is one important parameter for pathogen invasion.

Heiti verkefnis: Næmni fyrir sýkingum og náttúrulegt ónæmi
Verkefnisstjóri: Guðmundur H. Guðmundsson, Háskóla Íslands

Tegund styrks: Verkefnisstyrkur
Styrkár: 2013-2015
Fjárhæð styrks: 19,998 millj. kr. alls
Tilvísunarnúmer Rannís:  130202

Recently we found that 4-Phenyl Butyric Acid (PBA) induces cathelicidin expression in VA10 bronchial epithelial cell line and can counteract pathogen mediated down-regulation of innate immunity. In the project we defined thoroughly the PBA response in epithelial cells. Interestingly, the vitamin D receptor was found necessary for PBA mediated induction of the antimicrobial peptide LL-37 expression. With this project and recent clinical trials PBA can be viewed as a candidate compound for use against infection, alone or together with antibiotics. This could lead to diminished use of classical antibiotics and subsequently reduced selection for antibiotic resistant bacterial strains.

In another specific aim we defined the effects of glucocorticosteroids on the expression of innate immunity effectors in epithelia and monocytes. Notably the usage of steroids has been associated with secondary infections. We found steroid drugs to inhibit the expression of innate immunity effectors including antimicrobial peptide LL-37 (encoded of the human CAMP gene). We further showed that vitamin D3 could counteract the steroid downregulation of the CAMP gene. In conclusion, glucocorticosteroid treatment can compromise front line defenses with increased risk for secondary infections. Our results indicate that vitamin D3 could be included during steroid treatment to reduce the inhibition of steroids on innate immunity. In addition, this project opens for broader approaches using clinical material.

Further expression of several innate immune genes was analyzed during differentiations of lung epithelium. We detected different expression pattern for the different innate immune effectors at mRNA level. This indicates several regulatory circuits in front line defenses that will be our aim to resolve in our continued effort to understand developmental regulation of innate immunity. The benefits will be better understanding of health and disease with possibilities to develop treatment alternatives.

Main output of the project: 1) two published articles: a) Mol Immunol. 2014 Oct 27;63(2):530-539. doi: 10.1016/j.molimm.2014.10.007, and b) Immunobiology. 2016 Feb;221(2):245-52. doi: 10.1016/j.imbio.2015.09.001. 2) One PhD degree, Nikhil N. Kulkarni completed his PhD 2016. 3) Preliminary results on expression of innate immune effectors in differentiating lung epithelium. 











Þetta vefsvæði byggir á Eplica