Tài liệu Báo cáo khoa học: Lipopolysaccharide-evoked activation of p38 and JNK leads to an increase

Lipopolysaccharide-evoked activation of p38 and JNK

leads to an increase in ICAM-1 expression in Schwann

cells of sciatic nerves

Aiguo Shen1,*, Junling Yang2,*, Yangyang Gu3

, Dan Zhou4

, Linlin Sun2

, Yongwei Qin2

,

Jianping Chen2

, Ping Wang2

, Feng Xiao2

, Li Zhang2 and Chun Cheng1,2

1 Jiangsu Province Key Laboratory of Neuroregeneration, Nantong University, Jiangsu, China

2 Department of Microbiology and Immunology, Medical College, Nantong University, Jiangsu, China

3 Department of Surgery, RICH Hospital, Nantong, Jiangsu, China

4 Department of Biochemistry, Medical College of Nantong University, Jiangsu, China

Intercellular adhesion molecule-1 (ICAM-1, CD54) is a

cell-surface glycoprotein that belongs to the immuno￾globulin superfamily of adhesion molecules. Its struc￾ture comprises a cytoplasmic tail, a transmembranous

region, and five extracellular domains binding to the

b2-integrin counter-receptors lymphocyte function￾associated antigen-1 (LFA-1) and CD11b ⁄ CD18

(MAC-1) [1–4]. The ICAM-1 gene promoter⁄ enhancer

Keywords

intercellular adhesion molecule-1;

lipopolysaccharide; mitogen-activated

protein kinase; peripheral nervous system;

Schwann cell

Correspondence

C. Cheng, Jiangsu Province Key Laboratory

of Neurodegeneration, Nantong University,

19 Qi-xiu Road, Nantong, Jiangsu 226001,

China

Fax: +86 513 85051999

Tel: +86 513 85051999

E-mail: [email protected]

*These authors contributed equally to this

work

(Received 30 April 2008, revised 22 June

2008, accepted 27 June 2008)

doi:10.1111/j.1742-4658.2008.06577.x

Lipopolysaccharide is a major constituent of the outer membrane of

Gram-negative bacteria. It activates monocytes and macrophages to

produce cytokines such as tumor necrosis factor-a and interleukins IL-1b

and IL-6. These cytokines appear to be responsible for the neurotoxicity

observed in peripheral nervous system inflammatory disease. It has been

reported that, in the central nervous system, the expression level of inter￾cellular adhesion molecule-1 (ICAM-1) was dramatically upregulated in

response to LPS, as well as many inflammatory cytokines. ICAM-1 con￾tributes to multiple processes seen in central nervous system inflammatory

disease, for example migration of leukocytes to inflammatory sites, and

adhesion of polymorphonuclear cells and monocytes to central nervous sys￾tem cells. In the present study, we found that lipopolysacharide evoked

ICAM-1 mRNA and protein expression early at 1 h post-injection, and the

most significant increase was seen at 4 h. Immunofluorescence double-label￾ing suggested that most of the ICAM-1-positive staining was located in

Schwann cells. Using Schwann cell cultures, we demonstrated that ICAM-1

expression in Schwann cells is regulated by mitogen-activated protein

kinases, especially the p38 and stress-activated protein kinase ⁄ c-Jun

N-terminal kinase pathways. Thus, it is thought that upregulation of

ICAM-1 expression in Schwann cells may be important for host defenses

after peripheral nervous system injury, and reducing the biosynthesis of

ICAM-1 and other cytokines by blocking the cell signal pathway might

provide a new strategy against inflammatory and immune reaction after

peripheral nerve injury.

Abbreviations

CNS, central nervous system; ERK, extracellular signal-regulated kinase; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ICAM-1,

intercellular adhesion molecule-1; IL, interleukin; LFA-1, lymphocyte function-associated antigen-1; LPS, lipopolysaccharide; MAPK, mitogen￾activated protein kinase; MHC, major histocompatibility complex; NF-jB, nuclear factor jB; PNS, peripheral nervous system; SAPK ⁄ JNK,

stress-activated protein kinase ⁄ c-Jun N-terminal kinase; SCs, Schwann cells; TNF, tumor necrosis factor.

FEBS Journal 275 (2008) 4343–4353 ª 2008 The Authors Journal compilation ª 2008 FEBS 4343