Modulation of allergic inflammation in the lung by a peptide derived from mycobacteria tuberculosis chaperonin 60.1

Yanira de los Angeles Riffo Vasquez, Varsha Kanabar-Raivadera, Sandra Dhian Rudman, Rodrigo Rodrigues e-Lacerda, Francis Alexandre Wei Ming Man, David J. Jackson, Valerie Corrigall

Research output: Contribution to journalArticlepeer-review

Abstract

Background
We have previously demonstrated that M. tuberculosis chaperonin 60.1 inhibits leukocyte diapedesis and bronchial hyperresponsiveness in a murine model of allergic lung inflammation.

Methods
In the present study we have investigated the effect of a shorter peptide sequence derived from Cpn 60.1, named IRL201104, on allergic lung inflammation induced by ovalbumin (OVA) in mice, and by house dust mite (HDM) in guinea pigs, as well as investigating the action of IRL201104 on human cells in vitro.

Results
Pre‐treatment of mice or guinea pigs with IRL201104 inhibits the infiltration of eosinophils to the lung, cytokine release, and in guinea pig skin, inhibits allergen‐induced vascular permeability. The protective effect of intra‐nasal IRL201104 against OVA‐induced eosinophilia persisted for up to 20 days post treatment. Moreover, OVA‐sensitized mice treated intra‐nasally with 20 ng/kg of IRL201104 show a significant increase in the expression of the anti‐inflammatory molecule ubiquitin A20, and significant inhibition of the activation of NF‐κB in lung tissue. Our results also show that A20 expression was significantly reduced in blood leukocytes and ASM obtained from patients with asthma compared to cells obtained from healthy subjects which was restored after incubation with IRL201104 in vitro, when added alone, or in combination with LPS or TNF‐α in ASM.

Conclusions
Our results suggest that a peptide derived from mycobacterial Cpn60.1 has a long‐lasting anti‐inflammatory and immunomodulatory activity which may help explain some of the protective effects of TB against allergic diseases.
Original languageEnglish
Pages (from-to)1-29
JournalClinical and Experimental Allergy
DOIs
Publication statusE-pub ahead of print - 16 Dec 2019

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