TY - JOUR
T1 - Sulochrin inhibits eosinophil activation and chemotaxis
AU - Ohashi, H.
AU - Motegi, Y.
AU - Kita, H.
AU - Gleich, G. J.
AU - Miura, T.
AU - Ishikawa, M.
AU - Kawai, H.
AU - Fukamachi, H.
PY - 1998
Y1 - 1998
N2 - Objective: Because eosinophils likely play important roles in the pathophysiology of allergic diseases, specific inhibitors of eosinophils may be desirable to treat such diseases. To evaluate the capacity of a novel compound, sulochrin, as an inhibitor of eosinophilic inflammation, we examined the effects of this compound on various effector functions of eosinophils. Materials and methods: We examined the effects of sulochrin on degranulation of human eosinophils stimulated with platelet-activating factor (PAF) or Sepharose 4B beads coated with secretory IgA (sIgA) or IgG. The effects of sulochrin on other effector functions of human eosinophils, including superoxide anion (O2-) production, leukotriene (LT) C4 release, and interleukin (IL)-8 production induced by sIgA-beads were also studied. Finally, using PAF and LTB4 as chemoattractants, we evaluated the potency of sulochrin to inhibit eosinophil migration in vitro and in vivo. Results: Sulochrin inhibited EDN release by eosinophils stimulated with sIgA-beads, IgG-beads and PAF in a concentration-dependent manner; IC50 values were 0.75 μM, 0.30 μM and 0.03 μM. Eosinophil O2- production, LTC4 release, and IL-8 production were also inhibited by sulochrin. Furthermore, PAF-induced chemotaxis of human eosinophils and LTB4-induced chemotaxis of guinea pig eosinophils were abolished by 1 μM of sulochrin. Finally, sulochrin potently inhibited LTB4-induced infiltration of eosinophils into the skin of guinea-pig in vivo. Conclusions: These results suggest that sulochrin is a potent inhibitor of various effector functions of eosinophils. Sulochrin and its derivatives may be useful in the development of therapeutic approaches for patients with allergic diseases.
AB - Objective: Because eosinophils likely play important roles in the pathophysiology of allergic diseases, specific inhibitors of eosinophils may be desirable to treat such diseases. To evaluate the capacity of a novel compound, sulochrin, as an inhibitor of eosinophilic inflammation, we examined the effects of this compound on various effector functions of eosinophils. Materials and methods: We examined the effects of sulochrin on degranulation of human eosinophils stimulated with platelet-activating factor (PAF) or Sepharose 4B beads coated with secretory IgA (sIgA) or IgG. The effects of sulochrin on other effector functions of human eosinophils, including superoxide anion (O2-) production, leukotriene (LT) C4 release, and interleukin (IL)-8 production induced by sIgA-beads were also studied. Finally, using PAF and LTB4 as chemoattractants, we evaluated the potency of sulochrin to inhibit eosinophil migration in vitro and in vivo. Results: Sulochrin inhibited EDN release by eosinophils stimulated with sIgA-beads, IgG-beads and PAF in a concentration-dependent manner; IC50 values were 0.75 μM, 0.30 μM and 0.03 μM. Eosinophil O2- production, LTC4 release, and IL-8 production were also inhibited by sulochrin. Furthermore, PAF-induced chemotaxis of human eosinophils and LTB4-induced chemotaxis of guinea pig eosinophils were abolished by 1 μM of sulochrin. Finally, sulochrin potently inhibited LTB4-induced infiltration of eosinophils into the skin of guinea-pig in vivo. Conclusions: These results suggest that sulochrin is a potent inhibitor of various effector functions of eosinophils. Sulochrin and its derivatives may be useful in the development of therapeutic approaches for patients with allergic diseases.
KW - Chemotaxis
KW - Degranulation
KW - Eosinophil
KW - Inhibitor
KW - Sulochrin
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U2 - 10.1007/s000110050352
DO - 10.1007/s000110050352
M3 - Article
C2 - 9831326
AN - SCOPUS:0031784460
SN - 1023-3830
VL - 47
SP - 409
EP - 415
JO - Inflammation Research
JF - Inflammation Research
IS - 10
ER -