Bacterial Lipopolysaccharides Form Procollagen-Endotoxin Complexes That Trigger Cartilage Inflammation and Degeneration: Implications for the Development of Rheumatoid Arthritis
Lorenz W, Buhrmann C, Mobasheri A, Lueders C, Shakibaei M
Arthritis Res Ther. 2013;15:R111
Although the etiology of rheumatoid arthritis (RA) is unknown, animal and human data suggest that bacterial organisms play some role in the initiation and propagation of RA as well as other forms of arthritis, such as osteoarthritis.[1,2]
Lorenz and colleagues used an in vitro model of human chondrocytes to identify that the bacterial cell wall component lipopolysaccharide (LPS) appears to upregulate chondrocyte related inflammation. Specifically, they determined that LPS derived from Escherichia coli interacts with collagen in extracellular matrix. Furthermore, LPS appeared to trigger the NF-kappaB pathway of inflammation through interactions with toll-like receptor 4.
They concluded that LPS-mediated inflammation could play a role in joint injury in RA as well as osteoarthritis. They also suggested that their model could be used to investigate mechanisms, such as inhalation of LPS, that may lead to arthritis.
A bacterial trigger for RA is attractive for many reasons, including the possibility that it represents a modifiable risk factor to reduce the development of disease. Established and emerging data, including the recent identification of potential mechanisms through which Porphyromonas gingivalis and other organisms lead to RA-related autoimmunity to citrullinated proteins, are intriguing.[2,3] Still, much remains to be learned about the mechanisms through which bacteria or other organisms, such as viruses or fungi, induce autoimmunity and tissue injury.
Unanswered questions are whether microbes can create antigens that trigger autoimmunity through molecular mimicry, or by creating an inflammatory environment where self-proteins are more likely to become antigenic. Furthermore, as Lorenz and colleagues' findings seem to support, organisms could be a "second hit" that leads to amplification of inflammation and joint injury in individuals who have already developed autoimmunity or joint injury.
In their discussion and on the basis of previous work, Lorenz and colleagues mention that LPS-induced chondrocyte injury and inflammation could be a mechanism to explain the increased risk for RA in persons who live in damp environments. This is a controversial topic, and it is not clear that if LPS does indeed play a role in joint inflammation in human disease, it is from an inhaled source, given the abundance of LPS-producing bacteria resident on human mucosal surfaces. It is also not clear how LPS-induced chondrocyte inflammation relates to other types of inflammation in RA (eg, synovial fibroblast activation).
Nevertheless, these new findings from Lorenz and colleagues on the role of LPS in chondrocyte inflammation are intriguing. Hopefully, we will soon learn more about the mechanisms through which bacteria or other organisms can result in joint and other organ-injury autoimmune diseases as well as such conditions as osteoarthritis, and ultimately discover how modification of microbial factors could lead to disease prevention.
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Cite this: Kevin Deane. A Bacterial Cause for Arthritis? - Medscape - Jan 10, 2014.