Functionality and opposite roles of two interleukin 4 haplotypes in immune cells

Author(s)

Anovazzi, G. ; Medeiros, M. C. ; Pigossi, S. C. ; Finoti, L. S. ; Souza Moreira, T. M. ; Mayer, M. P. A. ; Zanelli, C. F. ; Valentini, S. R. ; Rossa-Junior, C. ; Scarel-Caminaga, R. M.

• Document type: Journal article
• Source: Genes and Immunity; v. 18, n. 1, p. 33-41, JAN-FEB 2017.
• Web of Science Citations: 3

Abstract

Cytokines expression can be influenced by polymorphisms in their respective coding genes. We associated the CTI/TTD haplotype (Hap-1) and TCl/CCI haplotype (Hap-2) in the 1L4 gene formed by the 590, +33 and variable number of tandem repeat polymorphisms with the severity of chronic periodontitis in humans. The functionality of these 1L4 haplotypes in the response of immune cells to phorbol 12-myristate 13-acetate (PMA) with lonomycin and IL-1 beta (as inflammatory stimuli) was evaluated. Gene expression (quantitative real-time PCR), profile of secreted cytokines (multiplex) and phenotypic polarization of T cells (flow cytometry) were the outcomes assessed. Green fluorescent protein reporter plasmid constructs containing specific IL4 haplotype were transiently transfected into JM cells to assess the influence of the individual haplotypes on promoter activity. In response to inflammatory stimuli the immune cells from Hap-1 haplotype had increased expression of anti-inflammatory IL4; conversely, the Hap-2 haplotype showed higher levels of pro-inflammatory cytokines. The haplotype CTI proved to be the most important for the regulation of 1L4 promoter, regardless of the nature of the inflammatory stimulation; whereas the polymorphism in the promoter region had the least functional effect. In conclusion, IL4 haplotypes studied are functional and trigger opposite immune responses: anti-inflammatory (Hap-1) and pro-inflammatory (Hap-2). In addition, we identified the CTI haplotype as the main responsible for the regulation of 1L4 transcriptional activity. (AU)

• FAPESP's process: 14/04638-2 - Investigation of the functional role of haplotypes in the interleukin 4 gene
• Grantee: Giovana Anovazzi Medeiros
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/17887-8 - Investigation of the functional role of haplotypes in the interleukin 4 and interleukin 8 genes
• Grantee: Raquel Mantuaneli Scarel Caminaga
• Support Opportunities: Regular Research Grants