Gene interactions and pathways from curated databases and text-mining
Endocrinology 2007, PMID: 17255201

Prolactin enhances interferon-gamma-induced production of CXC ligand 9 (CXCL9), CXCL10, and CXCL11 in human keratinocytes.

Kanda, Naoko; Watanabe, Shinichi

Psoriasis vulgaris is an autoimmune dermatosis characterized by type 1 T cell infiltration. Prolactin may be involved in the pathogenesis of psoriasis. CXC ligand 9 (CXCL9), CXCL10, and CXCL11 recruit type 1 T cells, and their production by keratinocytes is enhanced in psoriatic lesions. CXCL9, CXCL10, and CXCL11 production by keratinocytes depends on nuclear factor-kappaB (NF-kappaB) and signal transducer and activator of transcription (STAT)1 and that of CXCL11 depends on interferon (IFN)-regulatory factor (IRF)-1. We examined in vitro effects of prolactin on CXCL9, CXCL10, and CXCL11 production in human keratinocytes. Although prolactin alone was ineffective, it enhanced IFN-gamma-induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of STAT1, NF-kappaB, and IRF-1. Inhibitors of Janus kinase (JAK), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities. Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK. Prolactin modestly or IFN-gamma greatly induced tyrosine phosphorylation of STAT1, and both were suppressed by JAK inhibitor. Prolactin modestly or IFN-gamma greatly induced serine phosphorylation of STAT1, which was suppressed by MEK or p38 MAPK inhibitor, respectively. Prolactin induced phosphorylation of inhibitory kappaBalpha and NF-kappaB p65, which was suppressed by MEK inhibitor. These results suggest that prolactin may enhance IFN-gamma-induced CXCL9, CXCL10, and CXCL11 production in keratinocytes via activation of STAT1, NF-kappaB, and IRF-1 through JAK2 and MEK/ERK pathways. Prolactin may promote type 1 T cell infiltration into psoriatic lesions via these chemokines.

Diseases/Pathways annotated by Medline MESH: MAP Kinase Signaling System, Psoriasis
Document information provided by NCBI PubMed

Text Mining Data

CXCL10 → interferon-gamma: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9), CXCL10 , and CXCL11 in human keratinocytes "

CXCL10 → Prolactin: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9), CXCL10 , and CXCL11 in human keratinocytes "

CXCL11 → interferon-gamma: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9), CXCL10, and CXCL11 in human keratinocytes "

CXCL11 → Prolactin: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9), CXCL10, and CXCL11 in human keratinocytes "

CXCL10 → Prolactin: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9), CXCL10 , and CXCL11 in human keratinocytes "

CXC ligand 9 (CXCL9) → interferon-gamma: " Prolactin enhances interferon-gamma induced production of CXC ligand 9 (CXCL9) , CXCL10, and CXCL11 in human keratinocytes "

CXCL10 — prolactin: " We examined in vitro effects of prolactin on CXCL9, CXCL10 , and CXCL11 production in human keratinocytes "

CXCL10 → IFN-gamma: " Although prolactin alone was ineffective, it enhanced IFN-gamma induced secretion and mRNA expression of CXCL9, CXCL10 , and CXCL11 in parallel to the activation of STAT1, NF-kappaB, and IRF-1 "

CXCL11 → IFN-gamma: " Although prolactin alone was ineffective, it enhanced IFN-gamma induced secretion and mRNA expression of CXCL9, CXCL10, and CXCL11 in parallel to the activation of STAT1, NF-kappaB, and IRF-1 "

CXCL9 → IFN-gamma: " Although prolactin alone was ineffective, it enhanced IFN-gamma induced secretion and mRNA expression of CXCL9 , CXCL10, and CXCL11 in parallel to the activation of STAT1, NF-kappaB, and IRF-1 "

CXCL10 → MAPK: " Inhibitors of Janus kinase ( JAK ), p38 MAPK , and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10 , and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL10 → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10 , and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL11 → MAPK: " Inhibitors of Janus kinase ( JAK ), p38 MAPK , and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL11 → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

STAT1 → MAPK: " Inhibitors of Janus kinase ( JAK ), p38 MAPK , and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1 , and IRF-1 activities "

STAT1 → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1 , and IRF-1 activities "

IRF-1 → MAPK: " Inhibitors of Janus kinase ( JAK ), p38 MAPK , and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

IRF-1 → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL9 → MAPK/ERK kinase (MEK): " Inhibitors of Janus kinase ( JAK ), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9 , CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL9 → IFN-gamma: " Inhibitors of Janus kinase ( JAK ), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9 , CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

CXCL9 → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9 , CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

NF-kappaB → MAPK/ERK kinase (MEK): " Inhibitors of Janus kinase ( JAK ), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB , STAT1, and IRF-1 activities "

NF-kappaB → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB , STAT1, and IRF-1 activities "

prolactin- → MAPK/ERK kinase (MEK): " Inhibitors of Janus kinase ( JAK ), p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

prolactin- → Janus kinase ( JAK ): " Inhibitors of Janus kinase ( JAK ) , p38 MAPK, and MAPK/ERK kinase (MEK) suppressed prolactin- plus IFN-gamma induced CXCL9, CXCL10, and CXCL11 production and NF-kappaB, STAT1, and IRF-1 activities "

MAPK → IFN-gamma: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

ERK → MAPK: " Prolactin induced phosphorylation of JAK2 and ERK , whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

ERK → IFN-gamma: " Prolactin induced phosphorylation of JAK2 and ERK , whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

ERK → JAK1: " Prolactin induced phosphorylation of JAK2 and ERK , whereas IFN-gamma induced phosphorylation of JAK1 , JAK2, and p38 MAPK "

ERK → JAK2: " Prolactin induced phosphorylation of JAK2 and ERK , whereas IFN-gamma induced phosphorylation of JAK1, JAK2 , and p38 MAPK "

ERK → Prolactin: " Prolactin induced phosphorylation of JAK2 and ERK , whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

IFN-gamma → JAK1: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1 , JAK2, and p38 MAPK "

IFN-gamma → JAK2: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2 , and p38 MAPK "

JAK2 → MAPK: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

JAK2 → JAK1: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1 , JAK2, and p38 MAPK "

JAK2 → JAK2: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2 , and p38 MAPK "

JAK2 → Prolactin: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

Prolactin → MAPK: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

Prolactin → IFN-gamma: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2, and p38 MAPK "

Prolactin → JAK1: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1 , JAK2, and p38 MAPK "

Prolactin → JAK2: " Prolactin induced phosphorylation of JAK2 and ERK, whereas IFN-gamma induced phosphorylation of JAK1, JAK2 , and p38 MAPK "

STAT1 → IFN-gamma: " Prolactin modestly or IFN-gamma greatly induced tyrosine phosphorylation of STAT1 , and both were suppressed by JAK inhibitor "

STAT1 → JAK: " Prolactin modestly or IFN-gamma greatly induced tyrosine phosphorylation of STAT1 , and both were suppressed by JAK inhibitor "

IFN-gamma → JAK: " Prolactin modestly or IFN-gamma greatly induced tyrosine phosphorylation of STAT1, and both were suppressed by JAK inhibitor "

STAT1 → IFN-gamma: " Prolactin modestly or IFN-gamma greatly induced serine phosphorylation of STAT1 , which was suppressed by MEK or p38 MAPK inhibitor, respectively "

p65 → Prolactin: " Prolactin induced phosphorylation of inhibitory kappaBalpha and NF-kappaB p65 , which was suppressed by MEK inhibitor "

CXCL10 → IFN-gamma: " These results suggest that prolactin may enhance IFN-gamma induced CXCL9, CXCL10 , and CXCL11 production in keratinocytes via activation of STAT1, NF-kappaB, and IRF-1 through JAK2 and MEK/ERK pathways "

CXCL10 → prolactin: " These results suggest that prolactin may enhance IFN-gamma induced CXCL9, CXCL10 , and CXCL11 production in keratinocytes via activation of STAT1, NF-kappaB, and IRF-1 through JAK2 and MEK/ERK pathways "

CXCL10 → prolactin: " These results suggest that prolactin may enhance IFN-gamma induced CXCL9, CXCL10 , and CXCL11 production in keratinocytes via activation of STAT1, NF-kappaB, and IRF-1 through JAK2 and MEK/ERK pathways "

Manually curated Databases

No curated data.