Proinflammatory Cytokine Genes are Constitutively Overexpressed in the Heart in Experimental Systemic Lupus Erythematosus: A Brief Communication

Abstract

The heart is one of a number of organs that may be affected in systemic lupus erythematosus (SLE), a prototypic autoimmune disease. Potential anatomical sites of involvement include the myocardium, pericardium, endocardium, valves, conduction system and blood vessels that subserve the heart. Typically, the severity of cardiovascular disease in lupus correlates with the degree of systemic inflammation, which is mirrored by the level of C-reactive protein (CRP) in the plasma. C-reactive protein, in turn is regulated by proinflammatory cytokines, such as interleukins (ILs) 1beta and 6. These cytokines have been found in functionally and/or structurally damaged areas of the heart and have been implicated in disease pathogenesis. It has been assumed that the source of these putatively pathogenetically relevant cytokines in the compromised heart is infiltrating mononuclear cells. This study tests the hypothesis that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation. Using as the experimental model MRL/MpJ-Tnfrs6(lpr) (MRL-lpr/lpr) mice, which spontaneously manifest an autoimmune syndrome that has clinical features of SLE, we show that ventricular homogenates and ventricular cardiomyocytes constitutively overexpress genes encoding the proinflammatory cytokines IL-1beta, IL-6, IL-10, and gamma interferon. The results suggest the possibility that proinflammatory cytokines emanating from the heart may actually contribute to the high levels of CRP that appear to aid in predicting subsequent cardiac events. Viewed in this setting, CRP becomes a footprint of an ongoing pathogenic process mediated, in part, by the heart muscle itself.

Anti‐glycative and anti‐inflammatory effects of caffeic acid and ellagic acid in kidney of diabetic mice

“…IL-1b, IL-6 and TNF-a, pro-inflammatory cytokines, were central mediators for the regulation of several biomarkers such as C-reactive protein and von Willebrand factor, which consequently enhanced the progression of inflammation, endothelial dysfunction and coagulation in diabetes [26,27]. It has been indicated that overexpression of these cytokines exacerbates the severity of diabetes [4,26].…”

Intragraft gene expression profile associated with the induction of tolerance by allochimeric MHC I in the rat heart transplantation model

“…Accordingly, we suggest that the downregulation of IL-1 b in CsA 1 allochimeric peptide treatment may be related to the immunosuppressive function of allochimeric peptide. Although it has been assumed that the source of proinflammatory cytokines in the compromised heart is infiltrating mononuclear cells, recent study on MRL/MpJ-Tnfrs6lpr (MRLlpr/lpr) mice with autoimmune syndrome showed that ventricular homogenates and ventricular cardiomyocytes constitutively over express genes encoding the proinflammatory cytokines IL-1 b, IL-6, IL-10 and gamma interferon (Tomita et al, 2004). This indicates that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation (Tomita et al, 2004).…”

“…Although it has been assumed that the source of proinflammatory cytokines in the compromised heart is infiltrating mononuclear cells, recent study on MRL/MpJ-Tnfrs6lpr (MRLlpr/lpr) mice with autoimmune syndrome showed that ventricular homogenates and ventricular cardiomyocytes constitutively over express genes encoding the proinflammatory cytokines IL-1 b, IL-6, IL-10 and gamma interferon (Tomita et al, 2004). This indicates that cardiomyocytes per se may contribute to proinflammatory cytokine production in the setting of systemic inflammation (Tomita et al, 2004). Thus, the downregulation of the IL-1 b expression level observed in our study in CsA 1 allochimeric peptide treated animals may prevent or lower the extent of the systemic inflammation in the heart allograft.…”

“…Among genes downregulated at 1 day and 3 days posttransplantation in CsA 1 peptide treatment were proinflammatory cytokines such as Interleukin-1 beta (IL-1 b), the members of their receptor complexes (IL1r2, IL1nr), and cell adhesion molecules involved in the leukocyte adhesion cascade such as Selectin (Arstall et al, 1999;Batten et al, 1996;Bick et al, 1997;Chevrel et al, 2002;Finesterer, 2009;Ing et al, 1999;Kacimi et al, 1998;Li and Xiao, 2001;Libby et al, 1988;Libby, 1989, 1990;Loppnow et al, 1998;Long, 2001;Mountain et al, 2008;Muller-Werdan et al, 1998;Ono et al, 1998;Ozeren et al, 2003;Tomita et al, 2004;Ukimura et al, 2003;Westphal et al, 2008;Xia et al, 2006) (Table 2 and Fig. 2).…”

Antiinflammatory and antifibrogenic effects of s‐ethyl cysteine and s‐methyl cysteine in the kidney of diabetic mice

“…The results of our present study once again supports that SEC and SMC, two compounds naturally derived from Allium plants, are potent antidiabetic agents. IL-6 and TNF-alpha, proinflammatory cytokines, were central mediators for the regulation of several biomarkers such as c-reactive protein and von Willebrand factor [18,19], which consequently contributed to the progression of inflammation, endothelial dysfunction, and coagulation. Thus, the suppression on IL-6 and TNF-alpha could retard or alleviate inflammation and improve endothelial dysfunction.…”