The lack of PI3K gamma favors M1 macrophage polarization and does not prevent kidney diseases progression

Author(s):Show less -

Amano, Mariane T. ^{[1, 2]} ; Castoldi, Angela ^[1] ; Andrade-Oliveira, Vinicius ^[1] ; Latancia, Marcela T. ^{[1, 2]} ; Terra, Fernanda F. ^[1] ; Correa-Costa, Matheus ^[1] ; Breda, Cristiane N. S. ^[1] ; Felizardo, Raphael J. F. ^[1] ; Pereira, Welbert O. ^[3] ; da Silva, Marina B. ^[1] ; Miyagi, Mariana Y. S. ^[1] ; Aguiar, Cristhiane F. ^[1] ; Hiyane, I, Meire ; Silva, Joao S. ^[4] ; Moura, Ivan C. ^{[5, 6, 7]} ; Camara, Niels O. S. ^{[8, 9]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil

^[2] Hosp Sirio Libanes, Inst Sirio Libanes Ensino & Pesquisa, Rua Prof Daher Cutait 69, BR-01308060 Sao Paulo, SP - Brazil

^[3] Fac Israelita Ciencias Saude Albert Einstein, Sch Med, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Biochem & Immunol, FMRP, Sao Paulo - Brazil

^[5] Lab Cellular & Mol Mechanisms Hematol Disorders &, INSERM UMR 1163, Paris - France

^[6] Paris Descartes Sorbonne Paris Cite Univ, Paris - France

^[7] CNRS ERL 8254, Lab Excellence GR Ex, Imagine Inst, Paris - France

^[8] Univ Sao Paulo, Fac Med, Lab Renal Pathol, Sao Paulo - Brazil

^[9] Hiyane, Meire, I, Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil

• Document type: Journal article
• Source: International Immunopharmacology; v. 64, p. 151-161, NOV 2018.
• Web of Science Citations: 4

Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) are major concerns in worldwide public health, and their pathophysiology involves immune cells activation, being macrophages one of the main players of both processes. It is suggested that metabolic pathways could contribute to macrophage modulation and phosphatidylinositol-3 kinase (PI3K) pathway was shown to be activated in kidneys subjected to ischemia and reperfusion as well as unilateral ureteral obstruction (UUO). Although PI3K inhibition is mostly associated with anti-inflammatory response, its use in kidney injuries has been shown controversial results, which indicates the need for further studies. Our aim was to unveil the role of PI3K gamma in macrophage polarization and in kidney diseases development. We analyzed bone-marrow macrophages polarization from wild-type (WT) and PI3K gamma knockout (PI3K KO) animals. We observed increased expression of M1 (CD86, CCR7, iNOS, TNF, CXCL9, CXCL10, IL-12 and IL-23) and decreased of M2 (CD206, Arg-1, FIZZ1 and YM1) markers in the lack of PI3K gamma. And this modulation was accompanied by higher levels of inflammatory cytokines in PI3K KO M1 cells. PI3K KO mice had increased M1 in steady state kidneys, and no protection was observed in these mice after acute and chronic kidney insults. On the contrary, they presented higher levels of protein-to-creatinine ratio and Kim-1 expression and increased tubular injury. In conclusion, our findings demonstrated that the lack of PI3K gamma favors M1 macrophages polarization providing an inflammatory-prone environment, which does not prevent kidney diseases progression. (AU)

• FAPESP's process: 12/02270-2 - New cellular, molecular and immunological mechanisms involved in acute and chronic renal injury: the search for new therapeutical approaches
• Grantee: Niels Olsen Saraiva Câmara
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/09563-8 - Modulation of the mTOR pathway through Toll-like receptors activation in dendritic cells and their effects on sepsis
• Grantee: Marcela Teatin Latancia
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/10435-1 - THE INFLUENCE OF MTOR PATHWAY IN MACROPHAGE MODULATION AND ITS CONSEQUENCES IN EXPERIMENTAL CHRONIC KIDNEY DISEASE
• Grantee: Mariane Tami Amano
• Support Opportunities: Scholarships in Brazil - Post-Doctoral