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

页码：556 / 566

页数：11

共 73 条

[1] Interaction of CD44 with different forms of hyaluronic acid. Its role in adhesion and migration of tumor cells [J].