ABSTRACT
Psoriasis-specific proteins dysregulated in keratinocytes and involved in the pathophysiological process of psoriasis remains elusive. We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3-/-) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3-/- mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) the spontaneously tuning up of psoriasis signatures in keratinocytes through JNK pathway; and 2) neutrophil accumulation caused by the enhanced leukocyte-recruiting capacity associated with overexpression of S100A7-9 and CXCL-1, 8 in keratinocytes with impaired galectin-3 expression. Psoriasis-like skin inflammation is significantly improved in gal-3-/- mice both by inhibition of neutrophils accumulation with a selective CXCR2 antagonist of SB225002, and by intracutaneous injection of recombinant galectin-3. Overall, these findings offer promising galectin-3-related diagnostic and therapeutic resolutions of psoriasis.
Subject(s)
Biomarkers/metabolism , Galectin 3/metabolism , Inflammation/diagnosis , Keratinocytes/physiology , Neutrophils/immunology , Psoriasis/diagnosis , Skin/immunology , Animals , Cells, Cultured , Disease Models, Animal , Disease Progression , Galectin 3/administration & dosage , Galectin 3/genetics , Humans , Imiquimod , MAP Kinase Kinase 4/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Phenylurea Compounds/pharmacology , Receptors, Interleukin-8B/antagonists & inhibitors , Signal TransductionABSTRACT
OBJECTIVE: To discuss the influence of the rhizome of Cibotium barametz on the heamorheology index in mice with adjuvant arthritis and to compare the effect of raw medicinals with that of the processed ones. METHOD: Mice was injected with Freund's complete adjuvant on the rihgt behind foot to make model of adjuvant arthritis (AA). Hydroxyacrbamide tablets were orally administrated by mice with AA to make model of AA due to deficiency in the kidney (DK-AA). And then we determined the heamorheology index of the normal group, positive control group, AA group, DK-AA group and medicinals-treated groups. RESULT: In the groups of AA, and DK-AA, the heamorheology index, such as high shearing, middle shearing, low shearing, plasma viscosity, whole blood reduction viscosity, erythrocyte aggregation exponent, erythrocyte degeneration exponent, sedimentation, sedimentation equation K value, erythrocyte rigidity exponent, erythrocyte electrophoresis time, casson viscosity, casson yield stress, increased significantly. After treated with Cibotium barametz, the heamorheology index except red blood count, packed cell volume, fibrinogen decreased obviously to get normal. CONCLUSION: Rhizome of Cibotium barametz could promote heamorheology in mice with AA and DK-AA to exhibit effect of promoting blood circulation and remove blood stasis. The medicinal rhizomes processed with sand have the effect enhanced.
