Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic graft-versus-host disease often results in a combined deficiency of humoral and cell-mediated immunity. Clinical and experimental studies have suggested that the decrease in B cell responsiveness is due to a failure of B cell production in the bone marrow, intrinsic B cell defects, excessive suppressor T cell activity, and deficient T helper activity. In the present study, we analyze the basis of B cell immunodeficiency in C.B-20-->(C.B-20 x B10.D2)F1 animals afflicted with chronic GVHD. The initial decline in B cell production in the BM accounts for the early reduction in the number of B cells in the spleen and BM. Later, as B cells appear in near-normal numbers in the BM, the spleen and lymph node are repopulated by the newly derived B cells. Associated with the appearance of B cells in the BM and spleen is the ability to respond to lipopolysaccharide. In contrast, both B cell populations are severely diminished in their ability to proliferate in response to agar-derived mitogens to form colonies (CFU-B). The reduction in the CFU-B response is most likely a consequence of an inherent B cell defect, since purification of C.B-20-->F1 splenic B cells does not restore the colony-forming potential. Unlike BM and splenic B cells, LN B cells are unable to respond to either mitogen. Taken together, these results imply that a population of B cells derived from a distinct lineage and/or B cell maturation is defective in mice undergoing GVHD.
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PMID:The effect of chronic graft-versus-host disease on B cell development. 845 80

Roquinimex is an immunomodulator that can effectively inhibit the development of several autoimmune diseases in animal models, but the mechanism is still unknown. In this study, we investigated the effect of roquinimex on chronic graft-versus-host disease (GVHD) in mice, a well-established model for human systemic lupus erythematosus (SLE). Oral administration of roquinimex significantly suppressed the development of proteinuria and ameliorated nephritis symptoms in chronic GVHD mice. In addition, renal histopathology and immunohistochemistry studies revealed reduced glomerulonephritis and decreased IgG deposition in chronic GVHD mice treated with roquinimex. Chronic GVHD is characterized by a predominance of Th2 cytokines, and proinflammatory cytokines that also play an important role in the pathology of tissue damage. Therefore, we focused on the effect of roquinimex on cytokine production. Chronic GVHD mouse splenocytes exhibited severely reduced interferon (IFN)-gamma production in response to Concanavalin (Con A) stimulation and an overt Th2 skewness. Roquinimex treatment, however, induced IFN-gamma production and restored the Th1/Th2 cytokine balance, although only a minimal effect of roquinimex on interleukin (IL)-4 secretion was observed. The production of the proinflammatory cytokines TNF-alpha and IL-1 beta by peritoneal macrophages from lipopolysaccharide (LPS)-treated GVHD mice was significantly inhibited by roquinimex treatment. These data suggested that the beneficial effect of roquinimex on lupus might, at least in part, result from a restoration of Th1/Th2 cytokine balance and inhibition of inflammatory cytokine production.
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PMID:Roquinimex-mediated protection effect on the development of chronic graft-versus-host disease in mice is associated with induction of Th1 cytokine production and inhibition of proinflammatory cytokine production. 1795 Mar 63