CD44 and hyaluronic acid regulate in vivo iNOS expression and metalloproteinase activity in murine air-pouch inflammation

被引：11
作者：
Cabrera, PV [1 ]
Blanco, G [1 ]
Alaniz, L [1 ]
Greczanik, S [1 ]
Garcia, M [1 ]
Alvarez, E [1 ]
Hajos, SE [1 ]
机构：
[1] Univ Buenos Aires, Fac Farm & Bioquim, CONICET, IDEHU,Catedra Inmunol, RA-1113 Buenos Aires, DF, Argentina
来源：
INFLAMMATION RESEARCH | 2004年 / 53卷 / 10期
关键词：
CD44; hyaluronic acid; air-pouch; iNOS; metalloproteinases;
D O I：
10.1007/s00011-004-1295-8
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
Objective: To evaluate the effects of anti-CD44 IM7.8.1 antibody, HMW-HA and LMW-HA on leukocyte migration and adhesion, and the induction of proinflammatory mediators, in mouse air-pouch inflammation induced by zymosan. Methods: Leukocytes were obtained from zymosan-air pouches after the intra-pouch injection of anti-CD44 IM7.8.1, isotype control, HMW-HA, LMW-HA or PBS. TNF-alpha, IL-1beta and NOS mRNA were estimated in leukocytes by semi-quantitative RT-PCR. Matrix metalloproteinases (MMPs) from exudates were evaluated by zymography and Western Blot. Adhesion and migration of leukocytes were evaluated in HA-coated plates and Boyden chambers respectively. Results: IM7.8.1 decreased NOS mRNA levels and the activity of both MMP-9 and MMP-2 eight h after injection into zymosan air pouch while IM7.8.1, HMW-HA and LMW-HA had no effect on IL1-beta or TNF-alpha mRNA levels. Leukocytes from air pouch adhered to and migrated in vitro against both HMW-HA and LMW-HA. LMW-HA increased the number of leukocytes in the air pouch and NOS mRNA levels as compared to PBS injection. In contrast, HMW-HA decreased leukocyte count and reduced NOS mRNA levels. Paradoxically, the activity of both MMP-9 and MMP-2 was increased by HMW-HA and decreased by LMW-HA. Conclusions: Both CD44 and HA can modulate leukocyte migration and induction of proinflammatory mediators in mouse zymosan air pouch inflammation. IM7.8.1 had consistent anti-inflammatory effects, reducing NOS, MMP-9 and MMP-2. HMW-HA and LMW-HA were able to modulate both the induction of proinflammatory mediators and leukocyte count in the air pouch.
引用
收藏
页码：556 / 566
页数：11
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