Identifiers
macrophage migration inhibitory factor
HUGO:MIF hgnc_id:HGNC:7097 HGNC:7097 ENTREZ:4282 UNIPROT:P14174
macrophage migration inhibitory factor (glycosylation-inhibiting factor)
HUGO:MIF HGNC:7097 ENTREZ:4282 UNIPROT:P14174
HUGO:MIF

Maps_Modules
HMC:TUMOR_PROMOTING_INFLAMMATION
HMC:ACTIVATING_INVASION_AND_METASTASIS
 Cancer Associated Fibroblasts   / GROWTH_FACTORS_SIGNALING_PATHWAYS 
HMC:RESISTING_CELL_DEATH
 Regulated Cell Death   / APOPTOSIS 
 Innate Immunity   / IMMUNOSUPPRESSIVE_CYTOKINE_PATHWAYS 

References
CASCADE:MIF
PMID:12782713
CD74 mediates MIF stimulation of ERK-1/2 (p44/p42) phosphorylation and proliferation of CCL210 human lung fibroblasts.
PMID:20861157
MIF inhibits in CXCR2/CD74-dependent manner recruitment of CAFs to the growing tumor.
 MACROPHAGE 
 MDSC 
 NATURAL_KILLER 
CASCADE:TNF
CASCADE:IFNG
CASCADE:IL4
CASCADE:IL13
CASCADE:TLR2_4
PMID:9637476, PMID:10878343
MIF prevented the release of perforin granules by NK cells but not CTLs.
Tumor cells produce Macrophage Migration-Inhibitory Factor to Prevent Lysis by NK Cells.
PMID:18490733
MIF inhibits NK cell activity through a transcriptional down-regulation of NKG2D
PMID:16283355, PMID:12803886
MIF upregulates expression of TLR4 in macrothages via PU.1 (SPI1) activation
MIF signal transduction initiated by binding to CD74.
PMID:23390297
MIF deficiency or small-molecule inhibition reduces splenic MDSC immune suppression in tumor-bearing mice
PMID:8195715
TNF and INFG induce MIF secretion in macrophages, TLR4 signaling induces MIF expression.
MIF inhitits expression of M1 markers such as TNF, IL12p40, COX2, INOS, IRF-5, MHC-II, CD11c, CD80, CD86 and MIF induces expression of M2 markers as IL10, stabilin-1, MRC-1, CD23

References
in_re423( Innate Immunity  ):
PMID:20547845
TLR4 signaling downstream of HMGB1 induces secretion of IL10
PMID:16713974
RNAi-mediated knockdown of CREB, Fos, and Jun expression resulted in diminished TLR2-induced IL-10 production
GSK3B inhitits activation (DNA binding) of AP-1 factors.
JNK is a classical activator of AP1 transcription factors.
Inhibition of JNK downregulates IL10 expression. Probably via
AP1.
PMID:17404308
CSF1 upregulates expression of IL10 and CCL2 probably via CSF1R.
PMID:15749884
c-Maf binds to the ???206/???171 region in the IL-10 promoter and upregulates IL10 expression.
in_re485( Innate Immunity  ):
PMID:11875494
HMOX1 (HO1) mediates the inhibitory effect of IL10
on LPS-induced NOS2 (INOS) expression.
PMID:6357187, PMID:8871614
IL13 downregulates INOS activity via ILRA1/STAT6 pathway.
PMID:16127449
PPARG sumoilated by PIAS1/UbC9 prevents dissociation of the NCoR???HDAC3 complex fro promoters and
transrepresses NF-kB dependent expression NOS2, Ccl3, Ccl7, Cxcl10.
PMID:15644117, PMID:17260466
HMGB1 induces NO production probably via NFkB dependent upregulation of INOS expression.
PMID:17689680
STAT1 binds to INOS promoter and induces INOS expression and NO production downstream of IFNG in murine macrophages. Acetylation inhibits STAT1 binding to promotor.
PMID:11399519
STAT1, IRF1 and NF-kB interact with NOS2 promoter and cooperatively activate NOS2 expression in macrophages downstteam of IFNG.
PMID:23390297
MIF inhitits expression of M1 markers such as NOS2 (INOS).
PMID;PMID:20194441
HIF1 upregulates expression of INOS.
in_re558( Innate Immunity  ):
PMID:17485448
Inhibition of??? ???NFkB signaling downstream of??? ???ABIN3??? ???
inhibits expression of??? ???IL8,??? ???IL6,??? ???TNF,??? ???IL12
PMID:16413922
NFKBID (IkBNS) inhibit late phase (after 3h) of expression of proinflanotory cytokines
Il-12p40 (IL-12p40), Il-18 (IL-18) and Csf3 (G_CSF).
PMID:16243976
IRF4 downregulates expression of TNFa, IL12p40, IL6 probably via inhibition of NF-kB and JNK signaling pathways.
CSF1 downregulates TNF, IL-23p19, IL-12p40 expression probably via induction of acomulation of p50 homodimer and inhibition of p65/p50 NF-kB signaling.
CSF2 upregulates expression of TNF, and have positive influence on IL12p70 (p40+p35), IL23 (p40+p19) expression, probably via induction rapid IkBa degradetion, RELA nuclear translocation and formation p65/p50 heterodimers provided induction of NFkB signaling.
MIF inhitits expression of M1 markers such as IL12p40
in_re629( Innate Immunity  ):
HMOX1 (HO1) mediates IL-10-induced suppression
of MMP9 expression.
PMID:23390297, PMID:22461508
MIF signaling induces angiogenesis provavly via upregulation of MMP9, VEGF expression.
in_re631( Innate Immunity  ):
PMID:21372296
HMGB1 markedly increased the expression of the genes for VEGF, and TGFB1 in
peritoneal macrophages via TLR4-dependent mechanisms.
PMID:21765015
CSF2 upregulates VEGF expression via HIF1a specific inhibition of PHD2 increases VEGF production
in_re1031( Innate Immunity  ):
PMID:12907458
Bcl-3??? ???interacted with NF-??B p50,
both Bcl-3??? ???and p50??? ???were recruited to the TNF promoter,
BCL3??? ??? and??? ???p50??? ???NFkB recruitment to??? ???TNF ???promoter
prevents binding of??? ???p65/p50??? ???NFkB??? ???heterodimers
to??? ???TNF promotor and suppresses??? ???TNF ???expression
downstream of??? ???IL10.
PMID:15465827
BCL3 forms complex with HDAC1 and
repression of the TNF promoter by BCL3
requires Histone Deacetylase Activity.
BCL3 inhibits expression of TNF.
HMOX1 (HO1) mediates IL-10-induced suppression of TNF production.
PMID:16878026, PMID:14660645, PMID:15644117, PMID:10952726
Increased TNF expression downstream of HMGB1 is regulated via MYD88 and probably NFkB.
PMID:10754326
Human TNF-alpha gene has binding sites for NF-kappa B. By transient transfection,
NF-kappa B p65 and p50 synergistically activated the TNF-alpha promoter.
Although both the kappa B1 and kappa B3 sites bound transcriptionally active NF-kappa B p50/p65 heterodimers, only the kappa B1 site contributed to down-regulation by NF-kappa B p50 homodimers.
PMID:7594497
TGFB1 and IL10 dowregulate expression of TNF.
MIF inhitits expression of M1 markers such as TNF.
in_re1039( Innate Immunity  ):
MIF induces expression of M2 markers ARG1, IL10, stabilin-1, MRC-1, CD23.

1. MIF@INNATE_IMMUNE_CELL_Cytosol

1. MIF@default

1. CD74:​MIF@INNATE_IMMUNE_CELL_Membrane

1. rMIF@INNATE_IMMUNE_CELL_Cytosol → MIF@INNATE_IMMUNE_CELL_Cytosol
2. MIF@INNATE_IMMUNE_CELL_Cytosol → MIF@default
3. MIF@default + CD74@INNATE_IMMUNE_CELL_Membrane → CD74:​MIF@INNATE_IMMUNE_CELL_Membrane

1. gTNF@INNATE_IMMUNE_CELL_Cytosol → rTNF@INNATE_IMMUNE_CELL_Cytosol
2. gMRC1@MARKERS_MACROPHAGE → rMRC1@MARKERS_MACROPHAGE
3. gSTAB1@MARKERS_MACROPHAGE → rSTAB1@MARKERS_MACROPHAGE
4. gFCER2@MARKERS_MACROPHAGE → rFCER2@MARKERS_MACROPHAGE
5. CD11c*@INNATE_IMMUNE_CELL_Cytosol → CD11c*@INNATE_IMMUNE_CELL_Membrane
6. PRF1@SECRETORY_GRANULE → PRF1@default
7. ERK1/2*@INNATE_IMMUNE_CELL_Cytosol → ERK1/2*|​pho@INNATE_IMMUNE_CELL_Cytosol
8. gNKG2D*@INNATE_IMMUNE_CELL_Cytosol → rNKG2D*@INNATE_IMMUNE_CELL_Cytosol
9. CD80@INNATE_IMMUNE_CELL_Cytosol → CD80@INNATE_IMMUNE_CELL_Membrane
10. CD86@INNATE_IMMUNE_CELL_Cytosol → CD86@INNATE_IMMUNE_CELL_Membrane
11. gIL10@INNATE_IMMUNE_CELL_Cytosol → rIL10@INNATE_IMMUNE_CELL_Cytosol
12. gNOS2@INNATE_IMMUNE_CELL_Cytosol → rNOS2@INNATE_IMMUNE_CELL_Cytosol
13. gIL12p40*@INNATE_IMMUNE_CELL_Cytosol → rIL12p40*@INNATE_IMMUNE_CELL_Cytosol
14. gMMP9@INNATE_IMMUNE_CELL_Cytosol → rMMP9@INNATE_IMMUNE_CELL_Cytosol
15. gMHC class II*@INNATE_IMMUNE_CELL_Cytosol → rMHC class II*@INNATE_IMMUNE_CELL_Cytosol
16. gVEGFA@INNATE_IMMUNE_CELL_Cytosol → rVEGFA@INNATE_IMMUNE_CELL_Cytosol
17. SPI1@INNATE_IMMUNE_CELL_Cytosol → SPI1@INNATE_IMMUNE_CELL_Cytosol
18. gIRF5@INNATE_IMMUNE_CELL_Cytosol → rIRF5@INNATE_IMMUNE_CELL_Cytosol
19. gPTGS2@INNATE_IMMUNE_CELL_Cytosol → rPTGS2@INNATE_IMMUNE_CELL_Cytosol
20. PGE2@INNATE_IMMUNE_CELL_Cytosol → PGE2@default