IL-6→Proteoglycans→Interleukin-1→NAD→poly-ADP-ribose

• 18606685(IL-6): Two loci on chromosome 15 control experimentally induced arthritis through the differential regulation of IL-6 and lymphocyte proliferation.

  Using genetic linkage analysis of proteoglycan-induced arthritis (PGIA) , a murine model for rheumatoid arthritis , we identified two loci , Pgia8 and Pgia9 , on chromosome 15 (chr15) that appear to be implicated in disease susceptibility.

• 12594249(Proteoglycans): Combined autoimmune models of arthritis reveal shared and independent qualitative (binary) and quantitative trait loci.

  Collagen-induced arthritis (CIA) and proteoglycan-induced arthritis (PGIA) are murine models for rheumatoid arthritis both in terms of their pathology and genetics.

• 1728980(Interleukin-1): Interleukin-1 enhances the development of type II collagen-induced arthritis only in susceptible and not in resistant mice.

  The development of type II collagen-induced arthritis (CIA) in DBA/1 mice is readily accelerated by treatments with interleukin-1 beta (IL-1 beta).

• 10086388(NAD): Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin.

  Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation.

• 8147870(poly-ADP-ribose): Nitric oxide toxicity in islet cells involves poly(ADP-ribose) polymerase activation and concomitant NAD+ depletion.

  Previous studies have shown that DNA strand breaks are an early consequence of nitric oxide toxicity in pancreatic islet cells.