Creatine supplementation impairs airway inflammation in an experimental model of asthma involving P2 x 7 receptor

Author(s):Show less -

Garcia, Monique ^{[1, 2]} ; Santos-Dias, Alana ^[1] ; Lacerda Bachi, Andre Luis ^{[1, 3]} ; Oliveira-Junior, Manoel Carneiro ^[1] ; Andrade-Souza, Adilson Santos ^[1] ; Ferreira, Sergio Cesar ^[1] ; Jonco Aquino-Junior, Jefferson Comin ^[1] ; Almeida, Francine Maria ^[1] ; Rigonato-Oliveira, Nicole Cristine ^[1] ; Ligeiro Oliveira, Ana Paula ^[4] ; Baggio Savio, Luiz Eduardo ^[5] ; Coutinho-Silva, Robson ^[5] ; Mueller, Tobias ^[6] ; Idzko, Marco ^[7] ; Siepmann, Timo ^{[2, 8]} ; Vieira, Rodolfo Paula ^{[1, 9, 10, 11]}

Affiliation:Show less -

^[1] Brazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP - Brazil

^[2] Dresden Int Univ, Ctr Clin Res & Management Educ, Div Hlth Care Sci, Dresden - Germany

^[3] Fed Univ Sao Paulo UNIFESP, Dept Otorhinolaryngol, Sao Paulo - Brazil

^[4] Nove Julho Univ, Dept Biophoton, Sao Paulo - Brazil

^[5] Univ Fed Rio de Janeiro, Inst Biophys Carlos Chagas Filho, Rio De Janeiro - Brazil

^[6] Univ Hosp RWTH Aachen, Div Pneumol, Aachen - Germany

^[7] Univ Vienna, Dept Pneumol, Vienna - Austria

^[8] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Neurol, Dresden - Germany

^[9] Fed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP - Brazil

^[10] Univ Brasil, Postgrad Program Bioengn & Biomed Engn, Sao Paulo - Brazil

^[11] Anhembi Morumbi Univ, Sch Med, Sao Jose Dos Campos, SP - Brazil

• Document type: Journal article
• Source: European Journal of Immunology; v. 49, n. 6, p. 928-939, JUN 2019.
• Web of Science Citations: 1

Abstract

Creatine (Cr) is a substrate for adenosine triphosphate synthesis, and it is the most used dietary supplement among professional and recreative athletes and sportsmen. Creatine supplementation may increase allergic airway response, but the cellular and molecular mechanisms are unknown. We used murine model of OVA-induced chronic asthma and showed that Cr supplementation increased total proteins, ATP level, lymphocytes, macrophages, and IL-5 levels in BALF, as well as IL-5 in the supernatant of re-stimulated mediastinal lymph nodes. IL-5 and IL-13 expression by epithelial cells and by peribronchial leukocytes were increased by Cr. Cr augmented the expression of P2 x 7 receptor by peribronchial leukocytes and by epithelial cells, and increased the accumulation of eosinophils in peribronchial space and of collagen fibers in airway wall. In human cells, while Cr induced a release of ATP, IL-6, and IL-8 from BEAS-2B cells, whole blood cells, such as eosinophils, and CD4(+) T cells, P2 x 7 receptor inhibitor (A740003) reduced such effects, as denoted by reduced levels of ATP, IL-6, and IL-8. Therefore, Cr supplementation worsened asthma pathology due to activation of airway epithelial cells and peribronchial leukocytes, involving purinergic signaling. (AU)

• FAPESP's process: 14/12755-9 - Effects of aerobic physical training in obese asthmatic mice
• Grantee: Jefferson Comin Jonco Aquino Junior
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 12/16498-5 - Effect of low level laser therapy in experimental models of pulmonary chronic diseases
• Grantee: Ana Paula Ligeiro de Oliveira
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/14604-8 - Role of purinergic signaling in the antiinflammatory effects of aerobic training in a model of asthma induced by house dust mite
• Grantee: Manoel Carneiro de Oliveira Junior
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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