TLR4 is a receptor HMGB1 induced muscle dysfunction in myositis.  "We show that HMGB1 acts via TLR4 but not RAGE to accelerate muscle fatigue and to induce MHC-class I expression in vitro". [1]

Great article by Lundberg, Grundtman et al, shows that "HMGB-1 may serve as an inducer of MHC class I in muscle fibers as supported by the clinical data from patients with early disease. Furthermore, HMGB-1 may promote muscle weakness by modulating Ca2+ release; [Great article, short and sweet][2]  Lundberg, Grundtman et al, 2008 as found at http://www.hopkinsarthritis.org/physician-corner/acr-highlights/acr-2008/myositis-highlights-2008/#abstract2055.

"HMGB1 was significantly inversely correlated with decreased miRs [microRNAs] expression, which both promote muscle inflammation and degeneration in polymyosits. [3]

High-mobility group box protein 1 (HMGB1) is primarily a nuclear protein that is capable to translocate to the extracellular space and mediate inflammation (Harris et al., 2012). In patients with myositis, overexpression of HMGB1 has been demonstrated in muscle fibers, infiltrating mononuclear cells, and endothelial cells (Ulfgren et al., 2004). HMGB1 may have a dual role in the pathogenesis of myositis. This protein acts through TLR-4 receptor to up-regulate MHC class I expression in muscle fibers. Also, it impairs calcium release from the sarcoplasmic reticulum, thereby contributing to muscle fatigue (Grundtman et al., 2010; Zong et al., 2013). In contrast, some studies have shown that HMGB1 plays a role in skeletal muscle regeneration (De Mori et al., 2007; Vezzoli et al., 2011). All these findings highlight the role of the innate immune system in the pathogenesis of inflammatory myopathies and suggest that manipulating TLRs and HMGB1 pathways may be a reasonable strategy for development of novel therapies in the future.[4]

 

 

 

 

1. Zong M1, Bruton JD, TLR4 as receptor for HMGB1 induced muscle dysfunction in myositis. Ann Rheum Dis. 2013 Aug;72(8):1390-9. doi: 10.1136/annrheumdis-2012-202207. Epub 2012 Nov 12., as found at http://www.ncbi.nlm.nih.gov/pubmed/23148306

2. Lundberg, Grundtman et al, 2008 as found at http://www.hopkinsarthritis.org/physician-corner/acr-highlights/acr-2008/myositis-highlights-2008/#abstract2055.

3. Shu, Peng, et al  Elevated HMGB1 and Decreased Micrornas Expression in Polymyositis: Potential Contributions to Muscle Inflammation and Degeneration, Ann Rheum Dis 2014;73:577 doi:10.1136/annrheumdis-2014-eular.4025

4. Lahouti, Christopher-Stine et al, Polymyositis and Dermatomyositis: Novel Insights into the Pathogenesis and Potential Therapeutic Targets, Discovery Medicine June 2015 as found at http://www.discoverymedicine.com/Arash-H-Lahouti/2015/06/polymyositis-and-dermatomyositis-novel-insights-into-the-pathogenesis-and-potential-therapeutic-targets/

 

Se also articles:
 

2. Grundtman C, Bruton J, Yamada T, Ostberg T, Pisetsky DS, Harris HE, Andersson U, Lundberg IE, Westerblad H: Effects of HMGB1 on in vitro responses of isolated muscle fibers and functional aspects in skeletal muscles of idiopathic inflammatory myopathies. FASEB J. 2010, 24: 570-578. 10.1096/fj.09-144782.PubMed

3. Ulfgren AK, Grundtman C, Borg K, Alexanderson H, Andersson U, Harris HE, Lundberg IE: Down-regulation of the aberrant expression of the inflammation mediator high mobility group box chromosomal protein 1 in muscle tissue of patients with polymyositis and dermatomyositis treated with corticosteroids. Arthritis Rheum. 2004, 50: 1586-1594. 10.1002/art.20220.PubMed