PMID: 14620137 The impaired capacity of MIF-deficient macrophages to respond to LPS was shown to be due to reduced expression of TLR4, the signal-transducing molecule of the LPS receptor complex.

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).

PMID: 14620137 MIF has been shown to up-regulate TLR4 expression, to counter-regulate the immunosuppressive effects of glucocorticoids, to activate the extracellular signal-regulated kinase- 1/2 (ERK-1/2), to suppress p53 activity and to inhibit Jab-1/ CSN5 activity.

PMID: 14620137 MIF has been shown to up-regulate TLR4 expression, to counter-regulate the immunosuppressive effects of glucocorticoids, to activate the extracellular signal-regulated kinase- 1/2 (ERK-1/2), to suppress p53 activity and to inhibit Jab-1/ CSN5 activity. ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes. The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137 MIF has been shown to up-regulate TLR4 expression, to counter-regulate the immunosuppressive effects of glucocorticoids, to activate the extracellular signal-regulated kinase- 1/2 (ERK-1/2), to suppress p53 activity and to inhibit Jab-1/ CSN5 activity. ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes. The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137, 10734131 Transcription of the human Tlr4 gene was shown to be dependent on the activity of PU.1, a member of the Ets family of transcription factors (16).

PMID: 14620137 By contrast, expression of TLR2, a member of the TLR family of pattern-recognition receptors involved in the recognition of Gram-positive bacteria, was unchanged in MIF-deficient macrophages, as one might have predicted given the normal responses of these cells to Gram-positive bacteria and yeast particles.

PMID: 14620137 Glucocorticoids bind the corresponding receptors. Classically, glucocorticoids suppress cytokine production by immune cells.

PMID: 14620137 Classically, glucocorticoids suppress cytokine production by immune cells.

PMID: 14620137, 9006339 Systemic administration of LPS causes a rapid release of MIF from essentially all tissues, leading to profound depletion of the cellular pools of MIF, which are quickly restored by a robust induction of MIF mRNA and de novo synthesis of the MIF protein

PMID: 14620137, 7659164, 8755565, 10446857 By contrast, MIF production was induced when cells were exposed to low concentrations of glucocorticoids (17-19)

PMID: 14620137 As observed with many stimuli, MIF release in response to dexamethasone or cortisol was bell-shaped

PMID: 14620137 As observed with many stimuli, MIF release in response to dexamethasone or cortisol was bell-shaped

PMID: 14620137 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes.

PMID: 14620137, 10364264 MIF was found to induce rapid and sustained activation of the ERK-1/2 mitogen-activated protein kinase pathway and proliferation of quiescent fibroblasts (21)

PMID: 14620137, 10364264 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes. ERK-1/2-mediated induction of cPLA2 is one mechanism whereby MIF could override the inhibitory effects of steroids on synthesis of arachidonic acid induced by proinflammatory stimuli (21). The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137, 10364264 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes. ERK-1/2-mediated induction of cPLA2 is one mechanism whereby MIF could override the inhibitory effects of steroids on synthesis of arachidonic acid induced by proinflammatory stimuli (21). The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137, 10364264 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes.

PMID: 14620137, 9006339 Systemic administration of LPS causes a rapid release of MIF from essentially all tissues, leading to profound depletion of the cellular pools of MIF, which are quickly restored by a robust induction of MIF mRNA and de novo synthesis of the MIF protein

PMID: 14620137, 10364264 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes.

PMID: 14620137, 10364264 ERK-1/2 activation by MIF requires protein kinase A activation and results in the augmentation of cytoplasmic phospholipase A2 (cPLA2) activity and ensuing production of arachidonic acid, prostaglandins and leukotrienes.

PMID: 14620137 The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137 The protection afforded by MIF against apoptosis was found to require the sequential activation of ERK-1/2, cPLA2, cyclooxygenase-2 and prostaglandin E2.

PMID: 14620137 It revealed that MIF binds to Jab-1/CSN5 (for Jun activation domain-binding protein-1 and subunit 5 of the COP9 signalosome).

PMID: 14620137, 11089976 Jab1/ CSN5 is a co-activator of the transcription factor activator protein-1 (AP-1), which is implicated in cell growth, transformation and death. Therefore, MIF inhibits the positive regulatory effects of Jab1/CSN5 on AP-1 and JNK activities (24).

PMID: 14620137, 9006339 Systemic administration of LPS causes a rapid release of MIF from essentially all tissues, leading to profound depletion of the cellular pools of MIF, which are quickly restored by a robust induction of MIF mRNA and de novo synthesis of the MIF protein

PMID: 14620137 TNF-alpha binds its respective receptor.

PMID: 14620137 IFN-gamma binds its corresponding receptor.

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).

PMID: 14620137, 8195715, 9736745, 10722628 Gram-negative and Gram-positive bacteria, bacterial endotoxin (LPS) and exotoxins [toxic shock syndrome toxin-1 (TSST-1) and streptococcal pyrogenic exotoxin A (SPEA)], mycobacteria, malaria pigment and proinflammatory cytokines [tumour necrosis factor-a (TNF-a) and interferon-g (IFN-g) have been found to induce macrophages to release MIF (12-14).