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Calcium/calmodulin-dependent kinase II is required for platelet-activating factor priming.
Shock. 2005 Feb; 23(2):99-106.S

Abstract

Platelet-activating factor (PAF) primes the macrophage proinflammatory response to inflammatory stimuli, such as lipopolysaccharide (LPS). The cellular events responsible for this priming or reprogramming remain unresolved, but may occur through an increase in cytosolic calcium, inducing calcium/calmodulin-dependent kinase (CaMK) activation. To study this, differentiated THP-1 cells were used to study the effect of CaMK II and IV inhibition on PAF-induced reprogramming of TLR4-mediated events. LPS induced p38, ERK 1/2, and JNK/SAPK phosphorylation, NF-kappaB and AP-1 activation, and TNF-alpha and IL-10 production. PAF pretreatment selectively increased LPS-induced ERK 1/2, JNK/SAPK, NF-kappaB and AP-1 activation, and TNF-alpha production. Inhibition of CaMK II prevented PAF-induced priming of these events. Inhibition of CaMK IV prevented LPS-induced ERK 1/2, JNK/SAPK, NF-kappaB and AP-1 activation, and TNF-alpha production, but increased IL-10 production with or without PAF pretreatment. Neither CaMK II nor IV inhibition had any affect on p38 activity. These data suggest that the function of CaMK II is essential for PAF-induced macrophage priming. This priming event is mediated in part by modulation of ERK 1/2, JNK/SAPK, NF-kappaB, and AP-1 activation. CaMK IV, on the other hand, is not specific for priming by PAF and appears to have a direct link in TLR4-mediated events.

Authors+Show Affiliations

Department of Surgery, University of Washington, Seattle, WA 98104, USA. jcuschie@u.washington.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15665723

Citation

Cuschieri, Joseph, et al. "Calcium/calmodulin-dependent Kinase II Is Required for Platelet-activating Factor Priming." Shock (Augusta, Ga.), vol. 23, no. 2, 2005, pp. 99-106.
Cuschieri J, Bulger E, Garcia I, et al. Calcium/calmodulin-dependent kinase II is required for platelet-activating factor priming. Shock. 2005;23(2):99-106.
Cuschieri, J., Bulger, E., Garcia, I., Jelacic, S., & Maier, R. V. (2005). Calcium/calmodulin-dependent kinase II is required for platelet-activating factor priming. Shock (Augusta, Ga.), 23(2), 99-106.
Cuschieri J, et al. Calcium/calmodulin-dependent Kinase II Is Required for Platelet-activating Factor Priming. Shock. 2005;23(2):99-106. PubMed PMID: 15665723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcium/calmodulin-dependent kinase II is required for platelet-activating factor priming. AU - Cuschieri,Joseph, AU - Bulger,Eileen, AU - Garcia,Iris, AU - Jelacic,Sandra, AU - Maier,Ronald V, PY - 2005/1/25/pubmed PY - 2005/6/29/medline PY - 2005/1/25/entrez SP - 99 EP - 106 JF - Shock (Augusta, Ga.) JO - Shock VL - 23 IS - 2 N2 - Platelet-activating factor (PAF) primes the macrophage proinflammatory response to inflammatory stimuli, such as lipopolysaccharide (LPS). The cellular events responsible for this priming or reprogramming remain unresolved, but may occur through an increase in cytosolic calcium, inducing calcium/calmodulin-dependent kinase (CaMK) activation. To study this, differentiated THP-1 cells were used to study the effect of CaMK II and IV inhibition on PAF-induced reprogramming of TLR4-mediated events. LPS induced p38, ERK 1/2, and JNK/SAPK phosphorylation, NF-kappaB and AP-1 activation, and TNF-alpha and IL-10 production. PAF pretreatment selectively increased LPS-induced ERK 1/2, JNK/SAPK, NF-kappaB and AP-1 activation, and TNF-alpha production. Inhibition of CaMK II prevented PAF-induced priming of these events. Inhibition of CaMK IV prevented LPS-induced ERK 1/2, JNK/SAPK, NF-kappaB and AP-1 activation, and TNF-alpha production, but increased IL-10 production with or without PAF pretreatment. Neither CaMK II nor IV inhibition had any affect on p38 activity. These data suggest that the function of CaMK II is essential for PAF-induced macrophage priming. This priming event is mediated in part by modulation of ERK 1/2, JNK/SAPK, NF-kappaB, and AP-1 activation. CaMK IV, on the other hand, is not specific for priming by PAF and appears to have a direct link in TLR4-mediated events. SN - 1073-2322 UR - https://www.unboundmedicine.com/medline/citation/15665723/Calcium/calmodulin_dependent_kinase_II_is_required_for_platelet_activating_factor_priming_ L2 - https://doi.org/10.1097/01.shk.0000148075.19190.db DB - PRIME DP - Unbound Medicine ER -