The Th17/Treg Cytokine Imbalance in Chronic Obstructive Pulmonary Disease Exacerbation in an Animal Model of Cigarette Smoke Exposure and Lipopolysaccharide Challenge Association

Author(s):Show less -

Cervilha, Daniela A. B. ^[1] ; Ito, Juliana T. ^[1] ; Lourenco, Juliana D. ^[1] ; Olivo, Clarice R. ^{[1, 2]} ; Saraiva-Romanholo, Beatriz M. ^{[1, 2]} ; Volpini, Rildo A. ^[3] ; Oliveira-Junior, Manoel C. ^[4] ; Mauad, Thais ^[5] ; Martins, Milton A. ^[1] ; Tiberio, Iolanda F. L. C. ^[1] ; Vieira, Rodolfo P. ^{[6, 7, 8]} ; Lopes, Fernanda D. T. Q. S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Med, Lab Expt Therapeut LIM 20, Dept Med, Sao Paulo - Brazil

^[2] Univ City Sao Paulo, Dept Postgrad, Inst Med Assistance State Publ Servant, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Sch Med, Nephrol Dept, Sao Paulo - Brazil

^[4] Nove Julho Univ, Lab Pulm & Exercise Immunol, Sao Paulo - Brazil

^[5] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo - Brazil

^[6] Brazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos - Brazil

^[7] Fed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos - Brazil

^[8] Univ Brasil, Postgrad Program Bioengn & Biomed Engn, Sao Paulo - Brazil

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 9, FEB 13 2019.
• Web of Science Citations: 1

Abstract

We proposed an experimental model to verify the Th17/Treg cytokine imbalance in COPD exacerbation. Forty C57BL/6 mice were exposed to room air or cigarette smoke (CS) (12 +/- 1 cigarettes, twice a day, 30 min/exposure and 5 days/week) and received saline (50 mu l) or lipopolysaccharide (LPS) (1 mg/kg in 50 mu l of saline) intratracheal instillations. We analyzed the mean linear intercept, epithelial thickness and inflammatory profiles of the bronchoalveolar lavage fluid and lungs. We evaluated macrophages, neutrophils, CD4(+) and CD8(+) T cells, Treg cells, and IL-10(+) and IL-17(+) cells, as well as STAT-3, STAT-5, phospho-STAT3 and phospho-STAT5 levels using immunohistochemistry and IL-17, IL-6, IL-10, INF-gamma, CXCL1 and CXCL2 levels using ELISA. The study showed that CS exposure and LPS challenge increased the numbers of neutrophils, macrophages, and CD4(+) and CD8(+) T cells. Simultaneous exposure to CS/LPS intensified this response and lung parenchymal damage. The densities of Tregs and IL-17(+) cells and levels of IL-17 and IL-6 were increased in both LPS groups, while IL-10 level was only increased in the Control/LPS group. The increased numbers of STAT-3, phospho-STAT3, STAT-5 and phospho-STAT5(+) cells corroborated the increased numbers of IL-17(+) and Treg cells. These findings point to simultaneous challenge with CS and LPS exacerbated the inflammatory response and induced diffuse structural changes in the alveolar parenchyma characterized by an increase in Th17 cytokine release. Although the Treg cell differentiation was observed, the lack of IL-10 expression and the decrease in the density of IL10(+) cells observed in the CS/LPS group suggest that a failure to release this cytokine plays a pivotal role in the exacerbated inflammatory response in this proposed model. (AU)

• FAPESP's process: 12/15165-2 - Role of purinergic signaling and of SOCS-JAK-STAT signaling in the antiinflammatory effects of aerobic training in experimental models of asma and in asthmatic individuals
• Grantee: Rodolfo de Paula Vieira
• Support Opportunities: Research Grants - Young Investigators Grants