Monocyte cytokine synthesis in response to extracellular cell stress proteins suggests these proteins exhibit network behaviour

TY - JOUR

T1 - Monocyte cytokine synthesis in response to extracellular cell stress proteins suggests these proteins exhibit network behaviour

AU - Kaiser, Frank

AU - Steptoe, Andrew

AU - Thompson, Stephen

AU - Henderson, Brian

PY - 2014/1

Y1 - 2014/1

N2 - Human peripheral blood monocytes were exposed to single or pairs of cell stress proteins (CSPs), specifically Hsp10, Hsp27, Hsp60 and Hsp70-the former two having anti-inflammatory actions while the latter pair being assumed to be pro-inflammatory in activity. This study was to test if these proteins exhibited any network behaviour. To control for possible lipopolysaccharide contamination, polymyxin B was used. Surprisingly, at concentrations higher than 1 mu g/ml, polymyxin B itself could induce cytokine synthesis. A number of commercial sources of the molecular chaperones were tested, and marked variations in monocyte cytokine synthesis were found. All four CSPs stimulated the same profile of IL-1/IL-6 synthesis and IL-10/TNF-alpha synthesis although the kinetics of production of these two pairs of cytokines were very different. A key question was whether extracellular molecular chaperones exhibited network behaviour. To test this, monocytes were cultured with suboptimal concentrations of single CSP and pairs of CSP to look for additive, synergistic or antagonistic cell responses. The major finding was that pairs of molecular chaperones, including chaperones thought to stimulate monocyte cytokine synthesis, could produce significant antagonistic cellular responses. This demonstrates that extracellular CSPs constitute an additional potent layer within the complex cytokine network and furthermore suggests that monocytes have evolved to dampen their immune responses upon exposure to extracellular networks of CSPs-perhaps as a mechanism for protecting cells against detrimental cellular stress responses.

AB - Human peripheral blood monocytes were exposed to single or pairs of cell stress proteins (CSPs), specifically Hsp10, Hsp27, Hsp60 and Hsp70-the former two having anti-inflammatory actions while the latter pair being assumed to be pro-inflammatory in activity. This study was to test if these proteins exhibited any network behaviour. To control for possible lipopolysaccharide contamination, polymyxin B was used. Surprisingly, at concentrations higher than 1 mu g/ml, polymyxin B itself could induce cytokine synthesis. A number of commercial sources of the molecular chaperones were tested, and marked variations in monocyte cytokine synthesis were found. All four CSPs stimulated the same profile of IL-1/IL-6 synthesis and IL-10/TNF-alpha synthesis although the kinetics of production of these two pairs of cytokines were very different. A key question was whether extracellular molecular chaperones exhibited network behaviour. To test this, monocytes were cultured with suboptimal concentrations of single CSP and pairs of CSP to look for additive, synergistic or antagonistic cell responses. The major finding was that pairs of molecular chaperones, including chaperones thought to stimulate monocyte cytokine synthesis, could produce significant antagonistic cellular responses. This demonstrates that extracellular CSPs constitute an additional potent layer within the complex cytokine network and furthermore suggests that monocytes have evolved to dampen their immune responses upon exposure to extracellular networks of CSPs-perhaps as a mechanism for protecting cells against detrimental cellular stress responses.

KW - Cell stress proteins

KW - Cytokines

KW - Network

KW - behaviour

KW - Inflammation

KW - EARLY-PREGNANCY FACTOR

KW - POLYMYXIN-B

KW - MOONLIGHTING PROTEINS

KW - MOLECULAR CHAPERONES

KW - INDUCTION

KW - RECEPTOR

KW - ALPHA

KW - IDENTIFICATION

KW - INHIBITION

KW - EFFICACY

U2 - 10.1007/s12192-013-0440-0

DO - 10.1007/s12192-013-0440-0

M3 - Article

SN - 1355-8145

VL - 19

SP - 135

EP - 144

JO - CELL STRESS AND CHAPERONES

JF - CELL STRESS AND CHAPERONES

IS - 1

M1 - N/A

ER -