Browsing by Subject "systemic lupus erythematosus"
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Item Sex differences in toll like receptor 7-mediated renal injury in a murine model of autoimmune-induced hypertension(2020-05) D'Souza, Bradley M.; Mathis, Keisa W.; Hodge, Lisa M.; Phillips, Nicole R.Systemic lupus erythematosus (SLE) is a female-dominant autoimmune disease associated with hypertension. We confirmed that SLE develops later in life in male vs. female SLE mice (35 vs. [less than] 30 weeks), yet both sexes develop hypertension by 35 weeks. Renal injury is a factor in hypertensive female SLE mice only, so we aimed to investigate this latent sex difference. We hypothesized that increased toll-like receptor 7 (TLR7), an immune mediator that instigates tissue damage, promotes renal injury in female SLE mice. We found that renal cortical expression of TLR7 was indeed higher in female SLE mice. In a follow-up study we found that renal hemodynamics were impaired in female SLE mice, but not males. Our data suggest that while the hypertension in female SLE mice may be due to renal mechanisms, hypertension in males is not. Future studies will dissect sex-specific factors that should be considered when treating hypertensive patients with underlying autoimmunity.Item Should Renal Inflammation Be Targeted While Treating Hypertension?(Frontiers Media S.A., 2022-06-13) Chaudhari, Sarika; Pham, Grace S.; Brooks, Calvin D.; Dinh, Viet Q.; Young-Stubbs, Cassandra M.; Shimoura, Caroline G.; Mathis, Keisa W.Despite extensive research and a plethora of therapeutic options, hypertension continues to be a global burden. Understanding of the pathological roles of known and underexplored cellular and molecular pathways in the development and maintenance of hypertension is critical to advance the field. Immune system overactivation and inflammation in the kidneys are proposed alternative mechanisms of hypertension, and resistant hypertension. Consideration of the pathophysiology of hypertension in chronic inflammatory conditions such as autoimmune diseases, in which patients present with autoimmune-mediated kidney inflammation as well as hypertension, may reveal possible contributors and novel therapeutic targets. In this review, we 1) summarize current therapies used to control blood pressure and their known effects on inflammation; 2) provide evidence on the need to target renal inflammation, specifically, and especially when first-line and combinatory treatment efforts fail; and 3) discuss the efficacy of therapies used to treat autoimmune diseases with a hypertension/renal component. We aim to elucidate the potential of targeting renal inflammation in certain subsets of patients resistant to current therapies.Item The Impact of Travel Stressors on the Pathogenesis of Autoimmunity in Female Lupus Mice(2022-05) Dinh, Viet Q.; Mathis, Keisa W.; Ma, Rong; Cunningham, J. Thomas; Basha, RiyazPreliminary studies found that an established model of systemic lupus erythematosus, the female NZBWF1 mouse, developed heightened disease severity later in life when shipped to UNTHSC during summer due to travel stressors. We hypothesized that this was partly due to early life stress that the mice experienced, and that eliminating these stressors will attenuate disease severity. We measured biomarkers of disease severity in NZBWF1 mice that were shipped as adults and compared with mice that were shipped in early life along with mice that were not shipped at all. We found that long-term biomarkers were higher in adult travel mice compared to early life travel mice, that these biomarkers were higher in summer mice compared to winter mice, and that non-travelling mice had the highest levels. Our findings indicate that adulthood stress exacerbates disease progression in NZBWF1 mice, and that seasonal factors impacted lupus pathogenesis in these adult mice.