RESUMEN
Macrophages contribute to a continuous increase in blood pressure and kidney damage in hypertension, but their polarization status and the underlying mechanisms have not been clarified. This study revealed an important role for M2 macrophages and the YM1/Chi3l3 protein in hypertensive nephropathy in a mouse model of hypertension. Bone marrow cells were isolated from the femurs and tibia of male FVB/N (control) and transgenic hypertensive animals that overexpressed the rat form of angiotensinogen (TGM(rAOGEN)123, TGM123-FVB/N). The cells were treated with murine M-CSF and subsequently with LPS+IFN-γ to promote their polarization into M1 macrophages and IL-4+IL-13 to trigger the M2 phenotype. We examined the kidneys of TGM123-FVB/N animals to assess macrophage polarization and end-organ damage. mRNA expression was evaluated using real-time PCR, and protein levels were assessed through ELISA, CBA, Western blot, and immunofluorescence. Histology confirmed high levels of renal collagen. Cells stimulated with LPS+IFN-γ in vitro showed no significant difference in the expression of CD86, an M1 marker, compared to cells from the controls or the hypertensive mice. When stimulated with IL-4+IL-13, however, macrophages of the hypertensive group showed a significant increase in CD206 expression, an M2 marker. The M2/M1 ratio reached 288%. Our results indicate that when stimulated in vitro, macrophages from hypertensive mice are predisposed toward polarization to an M2 phenotype. These data support results from the kidneys where we found an increased infiltration of macrophages predominantly polarized to M2 associated with high levels of YM1/Chi3l3 (91,89%), suggesting that YM1/Chi3l3 may be a biomarker of hypertensive nephropathy.
Asunto(s)
Hipertensión/metabolismo , Enfermedades Renales/metabolismo , Lectinas/metabolismo , Macrófagos/metabolismo , beta-N-Acetilhexosaminidasas/metabolismo , Animales , Biomarcadores/metabolismo , Interleucina-13/metabolismo , Interleucina-4/metabolismo , Riñón/metabolismo , Enfermedades Renales/genética , Lectinas/genética , Activación de Macrófagos/fisiología , Masculino , Ratones , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , beta-N-Acetilhexosaminidasas/genéticaRESUMEN
BACKGROUND: Only a few studies have addressed the relationship between toll-like receptors 2 and 4 (TLR2 and TLR4) and the production of local and systemic cytokines in response to physical exercise, and they have produced conflicting results. We aimed to determine whether acute and chronic exercise outcomes are associated with changes in TLR2 and TLR4 expression and signaling and if so, the mechanisms that connect them. METHODS: PubMed database were consulted. This systematic review selected 39 articles, 26 involving humans and 13 based on rodents. RESULTS: In acute resistance exercise studies, 75% reported a decrease in TLR4 or TLR2 expression and 25% did not find differences. For chronic resistance exercise studies, 67% reported a reduction of expression and 33% did not find differences. Studies of both types reported reductions in pro-inflammatory cytokines. In acute aerobic exercise studies, 40% revealed a decline in the expression of the receptors, 7% reported no significant difference, 40% showed an increase, and 13% did not evaluate their expression. Fifty-eight percent of studies of chronic aerobic exercise revealed a reduction in expression, 17% did not find a difference, and 25% reported increases; they also suggested that the expression of the receptors might be correlated with that of inflammatory cytokines. In studies on combined exercise, 50% reported a decline in receptors expression and 50% did not find a difference. CONCLUSIONS: The majority of the articles (54%) link different types of exercise to a decline in TLR4 and TLR2 expression. However, aerobic exercise may induce inflammations through its influence on these receptor pathways. Higher levels of inflammation were seen in acute sessions (40%) than regular sessions (25%).
RESUMEN
Aim. Utilizing a cross-sectional case control design, the aim of this study was to evaluate the functional fitness and self-reported quality of life differences in older people diagnosed with knee osteoarthrosis (O) who participated in health promotion groups. Methods. Ninety older women were distributed into two groups: control without O of the knee (C, n = 40) and a group diagnosed with primary and secondary knee O with grade II or higher, with definite osteophytes (OA, n = 50). Functional fitness was evaluated by specific tests, and the time spent in physical activity and quality of life was evaluated by the IPAQ and WHOQOL (distributed in four domains: physical: P, psychological: PS, social: S, and environmental: E) domain questionnaires. Results. No differences were found between ages of groups (C: 66 ± 7; OA: 67 ± 9; years). The values of the chair stand test (rep) in the OA (13 ± 5) group were different when compared to C group (22 ± 5). For the 6-minute walk test (meters), the values obtained for the C (635 ± 142) were higher (P < 0.01) than the OA (297 ± 143) group. The time spent in physical activity (min) was greater (P < 0.001) in the control (220 ± 12) group compared to OA (100 ± 10) group. Higher values (P < 0.001) in all domains were found in the C (P: 69 ± 16, PS: 72 ± 17, S: 67 ± 15, E: 70 ± 15) group compared to OA (P: 48 ± 7, PS: 43 ± 8, S: 53 ± 13, E: 47 ± 14) group. Conclusion. Our data suggests that knee O, in older women, can promote a decline in time spent performing physical activity and functional fitness with decline in quality of life with an increase in sitting time.