Functionality of the Interleukin 8 haplotypes in lymphocytes and macrophages in response to gram-negative periodontopathogens

Author(s)

Pigossi, Suzane C. ^[1] ; Anovazzi, Giovana ^[1] ; Finoti, Livia S. ^[1] ; de Medeiros, Marcell C. ^[1] ; Mayer, Marcia P. A. ^[2] ; Rossa Junior, Carlos ^[1] ; Scarel-Caminaga, Raquel M. ^[3]

Affiliation

^[1] UNESP Sao Paulo State Univ, Sch Dent Araraquara, Dept Diag & Surg, Araraquara, SP - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo - Brazil

^[3] UNESP Sao Paulo State Univ, Sch Dent Araraquara, Dept Morphol, CP 331, BR-14801903 Araraquara, SP - Brazil

• Document type: Journal article
• Source: Gene; v. 689, p. 152-160, MAR 20 2019.
• Web of Science Citations: 1

Abstract

Individuals carrying the ATC/TTC haplotype (Hap-1) in the interleukin 8 (IL8) gene were reported as more susceptible to chronic periodontitis (CP), an infectious disease associated with Gram-negative bacteria, in comparison to patients with the ATT/TTC haplotype (Hap-2). This study investigated the functionality of the IL8 haplotypes in lymphocytes and monocytes of individuals carrying the Hap-1 or Hap-2 IL8 haplotypes in the response to CP-associated Gram-negative bacteria (periodontopathogens). Peripheral blood was collected from 6 subjects carrying each haplotype, and their immune cells were challenged with periodontopathogens or phorbol 12-myristate 13-acetate (PMA) plus Ionomycin. Depending on the immune cell type (lymphocytes or monocytederived macrophages) the assessed outcomes were: phenotypical polarization, gene expression, phagocytic activity, chemotaxis and production of reactive oxygen species (ROS). Subjects carrying the Hap-1 haplotype showed increased expression of IL8 and TNFA and significantly skewing towards pro-inflammatory Th1/M1/Th17 phenotypes. There was increased percentage of ROS-producing monocyte-derived macrophages from individuals carrying the Hap-1 haplotype. Cells from individuals presenting the Hap-2 haplotype had an overall attenuated response to periodontopathogens, with a significant shift towards the Treg phenotype. In conclusion, the IL8 haplotypes showed to be functional both in monocyte-derived macrophages and lymphocytes. The Hap-1 haplotype previously associated with increased susceptibility to CP demonstrated greater skewing to pro-inflammatory Th1/M1/Th17 phenotypes and production of ROS. (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