TY - JOUR
T1 - The actin cytoskeleton
T2 - An essential component for enhanced TNFα production by adherent monocytes
AU - Rosengart, Matthew R.
AU - Arbabi, Saman
AU - Bauer, Gregory J.
AU - Garcia, Iris
AU - Jelacic, Sandra
AU - Maier, Ronald V.
PY - 2002/2
Y1 - 2002/2
N2 - Monocyte adherence induces the formation of focal adhesions, the interaction sites of intracellular signaling molecules and cytoskeletal proteins such as actin. We previously demonstrated that adherence potentiates human monocyte LPS-induced TNFα production. Hence, we hypothesized that the actin cytoskeleton is integral to adherence-induced priming for enhanced LPS-induced TNFα production. In contrast to nonadherent cells, LPS induced significant transcription of TNFα mRNA and production of TNFα in adherent monocytes. Disrupting the actin cytoskeleton with cytochalasin D (CD) in adherent monocytes inhibited LPS-induced TNFα production by 55%, thereby abrogating adherence-induced priming. Moreover, CD pretreatment abrogated adherence-induced activation of Pyk2, a major focal adhesion kinase, and ERK 1/2, a component of the mitogen-activated protein kinase (MAPK) signaling pathway, and it completely inhibited LPS-induced ERK 1/2 activation. However, CD treatment of nonadherent monocytes failed to inhibit cytokine production. In conclusion, the actin cytoskeleton is integral in the reprogramming of the monocyte for enhanced cytokine production and in maintaining this "primed" state.
AB - Monocyte adherence induces the formation of focal adhesions, the interaction sites of intracellular signaling molecules and cytoskeletal proteins such as actin. We previously demonstrated that adherence potentiates human monocyte LPS-induced TNFα production. Hence, we hypothesized that the actin cytoskeleton is integral to adherence-induced priming for enhanced LPS-induced TNFα production. In contrast to nonadherent cells, LPS induced significant transcription of TNFα mRNA and production of TNFα in adherent monocytes. Disrupting the actin cytoskeleton with cytochalasin D (CD) in adherent monocytes inhibited LPS-induced TNFα production by 55%, thereby abrogating adherence-induced priming. Moreover, CD pretreatment abrogated adherence-induced activation of Pyk2, a major focal adhesion kinase, and ERK 1/2, a component of the mitogen-activated protein kinase (MAPK) signaling pathway, and it completely inhibited LPS-induced ERK 1/2 activation. However, CD treatment of nonadherent monocytes failed to inhibit cytokine production. In conclusion, the actin cytoskeleton is integral in the reprogramming of the monocyte for enhanced cytokine production and in maintaining this "primed" state.
KW - Cytokine
KW - Focal adhesions
KW - Lipopolysaccharide
KW - Microfilaments
KW - Mitogen-activated protein kinase
KW - Tyrosine kinase
UR - http://www.scopus.com/inward/record.url?scp=0036483605&partnerID=8YFLogxK
U2 - 10.1097/00024382-200202000-00005
DO - 10.1097/00024382-200202000-00005
M3 - Article
C2 - 11837785
AN - SCOPUS:0036483605
SN - 1073-2322
VL - 17
SP - 109
EP - 113
JO - Shock
JF - Shock
IS - 2
ER -