| Full text | |
| Author(s): Show less - |
Braga, Tarcio Teodoro
[1]
;
Correa-Costa, Matheus
[1]
;
Azevedo, Hatylas
[2]
;
Silva, Reinaldo Correia
[1]
;
Cruz, Mario Costa
[1]
;
Soares Almeida, Maira Estanislau
[3]
;
Hiyane, Meire Ioshie
[1]
;
Moreira-Filho, Carlos Alberto
[2]
;
Santos, Marinilce Fagundes
[3]
;
Perez, Katia Regina
[4]
;
Cuccovia, Iolanda Midea
[4]
;
Saraiva Camara, Niels Olsen
[1, 5, 6]
Total Authors: 12
|
| Affiliation: | [1] Univ Sao Paulo, Inst Biomed Sci 4, Dept Immunol, Lab Transplantat Immunobiol, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Pediat, Fac Med, FMUSP, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Cellular Biol, Sao Paulo - Brazil
[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Sao Paulo - Brazil
[5] Fed Univ Sao Paulo UNIFESP, Div Nephrol, Lab Clin & Expt Immunol, Sao Paulo - Brazil
[6] Univ Sao Paulo, Renal Pathophysiol Lab LIM16, Fac Med, Sao Paulo - Brazil
Total Affiliations: 6
|
| Document type: | Journal article |
| Source: | IMMUNITY INFLAMMATION AND DISEASE; v. 4, n. 3, p. 300-314, SEP 2016. |
| Web of Science Citations: | 1 |
| Abstract | |
IntroductionMacrophages are heterogeneous and thus can be correlated with distinct tissue outcomes after injury. Conflicting data have indicated that the M2-related phenotype directly triggers fibrosis. Conversely, we hypothesize here that the inflammatory milieu provided by early infiltration of pro-inflammatory macrophages dictates tissue scarring after injury. Methods and ResultsWe first determined that tissue-localized macrophages exhibit a pro-inflammatory phenotype (p40IL12(+)CCR7(+)CD11b(+)) during the early phase of a chronic injury model, in contrast to a pro-resolving phenotype (Arg1(+)IL10(+)CD206(+)CD11b(+)) at a later stage. Then, we evaluated the effects of injecting macrophages differentiated in vitro in the presence of IFN+LPS or IL4+IL13 or non-differentiated macrophages (hereafter, M0) on promoting inflammation and progression of chronic injury in macrophage-depleted mice. In addition to enhancing the expression of pro-inflammatory cytokines, the injection of M (IFN+LPS), but not M (IL4+IL13) or M0, accentuated fibrosis while augmenting levels of anti-inflammatory molecules, increasing collagen deposition and impairing organ function. We observed a similar profile after injection of sorted CCR7(+)CD11b(+) cells and a more pronounced effect of M (IFN+LPS) cells originated from Stat6(-/-) mice. The injection of M (IFN+LPS) cells was associated with the up-regulation of inflammation- and fibrosis-related proteins (Thbs1, Mmp7, Mmp8, and Mmp13). ConclusionsOur results suggest that pro-inflammatory macrophages promote microenvironmental changes that may lead to fibrogenesis by inducing an inflammatory milieu that alters a network of extracellular-related genes, culminating in tissue fibrosis. (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 |