Leptin antagonism attenuates hypertension and renal injury in an experimental model of autoimmune disease.
| Autor: | Kalusche WJ; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Case CT; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A., Taylor EB; Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS 39216, U.S.A. |
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| Jazyk: | angličtina |
| Zdroj: | Clinical science (London, England : 1979) [Clin Sci (Lond)] 2023 Dec 14; Vol. 137 (23), pp. 1771-1785. |
| DOI: | 10.1042/CS20230924 |
| Abstrakt: | Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that is characterized by B- and T-lymphocyte dysfunction and altered cytokine production, including elevated levels of the adipocytokine leptin. Leptin has various immunomodulatory properties, including promoting the expansion of proinflammatory T lymphocytes and the proliferation and survival of B cells. In the present study, we hypothesized that leptin antagonism would improve B- and T-cell dysfunction and attenuate hypertension in an experimental model of SLE, the NZBWF1 mouse. To test this hypothesis, 28-week-old female control and SLE mice were administered 5 mg/kg of murine leptin superantagonist (LA) or vehicle via ip injection every other day for four weeks. Analysis of peripheral blood immune cell populations showed no changes in total CD45R+ B and CD3+ T cell percentages after treatment with LA. However, SLE mice treated with LA had an improved CD4/CD8 ratio and decreased CD3+CD4-CD8- double negative (DN) T cells. Blood pressure was higher in SLE than in control, and treatment with LA decreased blood pressure in SLE mice. Treatment with LA also delayed the onset of albuminuria and decreased glomerulosclerosis in SLE mice. Renal immune cell infiltration was significantly higher in SLE mice as compared with control, but LA treatment was associated with decreased levels of renal CD4+ T cells. In conclusion, these data suggest that leptin plays a pathogenic role in the development of hypertension in SLE, in part, by promoting the expansion of inflammatory DN T cells and the infiltration of T cells into the kidneys. (© 2023 The Author(s).) |
| Databáze: | MEDLINE |
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