Tropomyosins in human diseases: ulcerative colitis.
Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD) that almost always affects the rectal mucosa and variable length of the colon in continuity and at times mucosa of the entire colon. It is not caused by any specific pathogen. Genetics, environmental factors and altered immune responses to dietary macromolecules, colonic bacteria and cellular proteins have been implicated in the pathogenesis of UC. Autoimmune response against cytoskeletal, microfilament protein tropomyosin (Tm) seems to play an important role in the pathogenesis of UC. The predominant colonic epithelial Tm isoform, hTm5, can induce both humoral (B-cells) and cellular (T-cells) response in patients with UC. Such responses are not seen in normal subjects and disease control subjects, such as patients with Crohn's disease (CD, another type of IBD) and patients with lupus. A novel observation that hTm5 is expressed on colon epithelial cell surface but not on small intestinal epithelial cells provides evidence for presentation to immune effector cells. This surface expression of hTm5 seems to be facilitated by a colon epithelial cell membrane associated protein, CEP, that acts as a chaperone for the trans-migration of hTm5 to the surface and both hTm5 and CEP are then released outside the cell. Both CEP and hTm5 expression are increased with pro-inflammatory cytokine, such as gamma-interferon. hTm5 expression in UC mucosa is also significantly increased compared to normal. Finally, autoantibodies against hTm5 observed both in circulation and in the colon mucosa of patients with UC are pathogenic causing colon epithelial cell destruction by antibody and complement mediated cytolysis.
Das
Kiron M
KM
Division of Gastroenterology and Hepatology, Department of Medicine, Crohn's and Colitis Center of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA. daskm@umdnj.edu
Bajpai
Manisha
M
D000818:Animals; D001324:Autoantigens / Q000737:chemistry; D015551:Autoimmunity; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003106:Colon / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism / Q000382:microbiology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005192:Family Health; D006801:Humans; D007107:Immune System; D007249:Inflammation; D008954:Models, Biological; D014335:Tropomyosin / Q000378:metabolism / Q000502:physiology*
D001324:Autoantigens; D016207:Cytokines; C498783:TPM3 protein, human; D014335:Tropomyosin