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Caveolin-1 (CAV-1) is the principal component of caveolae that regulates a variety of signaling molecules and receptors. Our previous study revealed CAV-1 reduction in the epidermis of patients with psoriasis, which leads to enhanced Janus kinase/signal transducer and activator of transcription activation and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. We observed that CAV-1 level in psoriasis patients was apparently reduced in peripheral blood mononuclear cells (PBMCs) and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes represented elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity. In a murine model of psoriasis-like inflammation induced by imiquimod, we observed a significant CAV-1 reduction in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.

Scleroderma-associated pulmonary fibrosis (SSc-PF) and idiopathic pulmonary fibrosis (IPF) are two of many chronic fibroproliferative diseases that are responsible for nearly 45% of all deaths in developed countries. While sharing several pathobiological characteristics, they also have very distinct features. Currently no effective anti-fibrotic treatments exist that can halt the progression of PF or reverse it. Our goal is to uncover potential gene targets for the development of anti-fibrotic therapies efficacious in both diseases, and those specific to SSc-PF, by identifying universal pathways and molecules driving fibrosis in SSc-PF and IPF tissues as well as those unique to SSc-PF. Using DNA microarray data, a meta-analysis of the differentially expressed (DE) genes in SSc-PF and IPF lung tissues (diseased vs. normal) was performed followed by a full systems level analysis of the common and unique transcriptomic signatures obtained. Protein-protein interaction networks were generated to identify hub proteins and explore the data using the centrality principle. Our results suggest that therapeutic strategies targeting IL6 trans-signaling, IGFBP2, IGFL2, and the coagulation cascade may be efficacious in both SSc-PF and IPF. Further, our data suggest that the expression of matrikine-producing collagens is also perturbed in PF. Lastly, an overall perturbation of bioenergetics, specifically between glycolysis and fatty acid metabolism, was uncovered in SSc-PF. Our findings provide insights into potential targets for the development of anti-fibrotic therapies that could be effective in both IPF and SSc-PF.

As an index of lipid peroxidation (LPO), levels of thiobarbituric acid (TBA)-reactive substances were examined in the kidneys of male F344 rats, BDFI, CDFI, and B6C3F1 mice, and Syrian golden hamsters after a single intravenous (IV) administration of potassium bromate (KBrO,) at various doses. In the rats, LPO levels were significantly increased in both a dose-dependent and time-dependent manner. However, when the rats were given intraperitoneal (IP) injection of cysteine, the levels of LPO were not significantly different between KBrO,-treated animals and controls. In CDFI mice, the slight increases in LPO levels observed were much weaker and not statistically significant. On the other hand, treatment of BDFl and B6C3F1 mice or hamsters with KBrO, resulted in decreased values as compared to controls. The effect of treatment with cysteine, glutathione (GSH), or diethyl maleate (DEM) on mortality was tested in male F344 rats given IV injection of KBrO, at various doses. Significant reduction and elevation in the mortality were observed in rats treated with cysteine or GSH and DEM, respectively. Significant dose-dependent and time-dependent increases were observed in the levels of serum nonprotein nitrogen (NPN), blood urea nitrogen (BUN), and creatinine, and absolute and relative weight of the kidneys in male F344 rats administered KBrO, IV. Microscopically, the appearance of numerous eosinophilic droplets in the cytoplasm of proximal tubular epithelium of KBr0,-treated rats was noteworthy. All these changes were reduced and exacerbated by treatment with cysteine or GSH and DEM, respectively. The possibility of LPO formation in the kidney by active oxygen radicals generated by KBrO, is suggested. A possible relationship between LPO levels in the kidney and species differences in the renal toxicity and carcinogenicity of KBrO, is implicated.