Background Activation of innate immune plays important role in the pathogenesis of autoimmune disease. Nod-like receptors (NLRs) are cytosol-expressed pattern recognition receptors that can sense endogenous cellular products associated with tissue injury . The activation of NLRs causes the formation and activation of inflammasomes, which are multi-protein platforms that mediate the activation of caspase-1, which can activate IL-1β[2,3]. Caspase-1 and IL-1b similarly distributed in muscles of dermatomyositis (DM) and polymyositis (PM) patients, suggesting a role of capase-1 in these diseases .
Objectives Our study was to investigate the expression of inflammasomes in muscle of DM and PM patients.
Methods Immunohistochemistry was performed to determine the expression of NALP (NACHT-LRR-PYD-containing protein)1, NALP3, ASC (apoptosis-associated speck-like protein containing a CARD) and caspase-1 in muscle of 10 newly diagnosed and untreated adult DM/PM patients (4 DM and 6 PM) and 5 healthy controls.
Results In muscle of 4 DM patients, ASC and caspase-1 were expressed in the plasma of CD3+ T and CD20+ B cells, while in 2 of them NALP3 was also expressed. Only 1 PM patient in 6 expressed NALP3, ASC and caspase-1 in the plasma of CD3+ T and CD20+ B cells. NALP1 was not expressed in all of the 10 patients. No NALP1, NALP3, ASC and caspase-1 were expressed in the muscle of 5 healthy controls. The positive rate of ASC and caspase-1 in DM group was significantly higher than that in PM and control group (P<0.01 and P<0.05), while the positive rate of NALP3 in DM group had no difference with that in PM and control group. The level of creatine kinase, erythrocyte sedimentation rate, C-reactive protein had no difference between NALP3, ASC and caspase-1 positive group and negative group.
Conclusions Innate immune plays different role in the pathogenesis of DM and PM. Inflammasome participates in the inflammation of DM but not in PM, and may be activated by NALP3.
Franchi L, McDonald C, Kanneganti TD, et al. Nucleotide-binding oligomerization domain-like receptors: intracellular pattern recognition molecules for pathogen detection and host defense. J Immunol, 2006, 177(6): 3507-3513.
Petrilli V, Dostert C, Muruve DA, et al. The inflammasome: a danger sensing complex triggering innate immunity. Curr Opin Immunol, 2007, 19(6): 615-622.
Yu HB, Finlay BB. The caspase-1 inflammasome: a pilot of innate immune responses. Cell Host Microbe, 2008, 4(3): 198-208.
Mackiewicz Z, Hukkanen M, Povilenaite D, et al. Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies. Clin Exp Rheumatol, 2003, 21(1): 41-48.
Acknowledgements The authors thank Dr. Pan Lin for her assistance with immunohistochemistry staining and Dr. Yaowen Zhang for statistical analysis.
Disclosure of Interest None declared