Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0019209 (
hepatomegaly
)
5,798
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The absence of tumor necrosis factor (TNF) causes lethal infection by
Leishmania major
in normally resistant C57BL/6J (B6.WT) mice. The underlying pathogenic mechanism of this fatal disease has so far remained elusive. We found that B6.WT mice deficient for the
tnf
gene (B6.TNF
-/-
) displayed not only a non-healing cutaneous lesion but also a serious infection of the liver upon
L. major
inoculation. Infected B6.TNF
-/-
mice developed an
enlarged liver
that showed increased inflammation. Furthermore, we detected an accumulating monocyte-derived macrophage population (CD45
+
F4/80
+
CD11b
hi
Ly6C
low
) that displayed a M2 macrophage phenotype with high expression of
CD206
, arginase-1, and IL-6, supporting the notion that IL-6 could be involved in M2 differentiation. In
in vitro
experiments, we demonstrated that IL-6 upregulated M-CSF receptor expression and skewed monocyte differentiation from dendritic cells to macrophages. This was countered by the addition of TNF. Furthermore, TNF interfered with the activation of IL-6-induced gp130-signal transducer and activator of transcription (STAT) 3 and IL-4-STAT6 signaling, thereby abrogating IL-6-facilitated M2 macrophage polarization. Therefore, our results support the notion of a general role of TNF in the inflammatory activation of macrophages and define a new role of IL-6 signaling in macrophage polarization downstream of TNF.
...
PMID:Absence of Tumor Necrosis Factor Supports Alternative Activation of Macrophages in the Liver after Infection with
Leishmania major
. 2940 88
