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| IJCEM Copyright © 2008-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Int J Clin Exp Med 2(1),48-67;2009
Review Article
MAP kinase phosphatase-1, a critical negative regulator of the innate immune
response
Liwu Li, Shuang-Feng Chen, Yusen Liu
Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA; Department of Laboratory Medicine, Liaocheng People’s
Hospital, Liaocheng, Shandong, China; Center for Perinatal Research, Children’s Research Institute, Columbus Children’s Hospital,
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
Received Feburary 3, 2009; accepted Feburary 13, 2009; available online February 15, 2009
Abstract: Mitogen-activated protein (MAP) kinase cascades are crucial signal transduction pathways in the regulation of the host
inflammatory response to infection. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, plays a pivotal role in
the deactivation of p38 and JNK. In vitro studies using cultured macrophages have provided compelling evidence for a central role of
MKP-1 in the restraint of pro-inflammatory cytokine biosynthesis. Studies using MKP-1 knockout mice have strengthened the findings
from in vitro studies and defined the critical importance of MKP-1 in the regulation of pro-inflammatory cytokine synthesis in vivo during
the host response to bacterial cell wall components. Upon challenge with Toll-like receptor ligands MKP-1 knockout mice produced
dramatically greater amounts of inflammatory cytokines, developed severe hypotension and multi-organ failure, and exhibited a
remarkable increase in mortality. More recent investigations using intact bacteria confirmed these observations and further revealed
novel functions of MKP-1 in host defense against bacterial infection. These studies demonstrate that MKP-1 is an essential feedback
regulator of the innate immune response, and that it plays a critical role in preventing septic shock and multi-organ dysfunction during
pathogenic infection. In this review, we will summarize the studies on the function of MKP-1 in innate immune responses and discuss
the regulation of this novel protein phosphatase. (IJCEM902001).
Key Words: MAP kinase, phosphatase-1, negative regulator, innate immune response, cytokines, inflammation
Full Text PDF
Address all correspondence to:
Yusen Liu, PhD
Center for Perinatal Research
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive
Columbus, Ohio 43205
USA
Tel: (614) 722-3073; Fax: (614) 355-3455
E-mail: yusen.liu@nationwidechildrens.org
Review Article
MAP kinase phosphatase-1, a critical negative regulator of the innate immune
response
Liwu Li, Shuang-Feng Chen, Yusen Liu
Department of Biological Sciences, Virginia Tech, Blacksburg, Virginia, USA; Department of Laboratory Medicine, Liaocheng People’s
Hospital, Liaocheng, Shandong, China; Center for Perinatal Research, Children’s Research Institute, Columbus Children’s Hospital,
Department of Pediatrics, The Ohio State University College of Medicine, Columbus, Ohio, USA
Received Feburary 3, 2009; accepted Feburary 13, 2009; available online February 15, 2009
Abstract: Mitogen-activated protein (MAP) kinase cascades are crucial signal transduction pathways in the regulation of the host
inflammatory response to infection. MAP kinase phosphatase (MKP)-1, an archetypal member of the MKP family, plays a pivotal role in
the deactivation of p38 and JNK. In vitro studies using cultured macrophages have provided compelling evidence for a central role of
MKP-1 in the restraint of pro-inflammatory cytokine biosynthesis. Studies using MKP-1 knockout mice have strengthened the findings
from in vitro studies and defined the critical importance of MKP-1 in the regulation of pro-inflammatory cytokine synthesis in vivo during
the host response to bacterial cell wall components. Upon challenge with Toll-like receptor ligands MKP-1 knockout mice produced
dramatically greater amounts of inflammatory cytokines, developed severe hypotension and multi-organ failure, and exhibited a
remarkable increase in mortality. More recent investigations using intact bacteria confirmed these observations and further revealed
novel functions of MKP-1 in host defense against bacterial infection. These studies demonstrate that MKP-1 is an essential feedback
regulator of the innate immune response, and that it plays a critical role in preventing septic shock and multi-organ dysfunction during
pathogenic infection. In this review, we will summarize the studies on the function of MKP-1 in innate immune responses and discuss
the regulation of this novel protein phosphatase. (IJCEM902001).
Key Words: MAP kinase, phosphatase-1, negative regulator, innate immune response, cytokines, inflammation
Full Text PDF
Address all correspondence to:
Yusen Liu, PhD
Center for Perinatal Research
The Research Institute at Nationwide Children’s Hospital
700 Children’s Drive
Columbus, Ohio 43205
USA
Tel: (614) 722-3073; Fax: (614) 355-3455
E-mail: yusen.liu@nationwidechildrens.org
