Macrophage regulation of graft-vs-host disease.

Hematopoietic stem cell transplantation has become a curative choice of many hematopoietic malignancy, but graft-vs-host disease (GVHD) has limited the survival quality and overall survival of hematopoietic stem cell transplantation. Understanding of the immune cells' reaction in pathophysiology of GVHD has improved, but a review on the role of macrophages in GVHD is still absent. Studies have observed that macrophage infiltration is associated with GVHD occurrence and development. In this review, we summarize and analyze the role of macrophages in GVHD based on pathophysiology of acute and chronic GVHD, focusing on the macrophage recruitment and infiltration, macrophage polarization, macrophage secretion, and especially interaction of macrophages with other immune cells. We could conclude that macrophage recruitment and infiltration contribute to both acute and chronic GVHD. Based on distinguishing pathology of acute and chronic GVHD, macrophages tend to show a higher M1/M2 ratio in acute GVHD and a lower M1/M2 ratio in chronic GVHD. However, the influence of dominant cytokines in GVHD is controversial and inconsistent with macrophage polarization. In addition, interaction of macrophages with alloreactive T cells plays an important role in acute GVHD. Meanwhile, the interaction among macrophages, B cells, fibroblasts, and CD4+ T cells participates in chronic GVHD development.

[Effects of electroacupuncture at neiguan (PC6) on c-Jun NH2-teminal kinase signaling pathways in hypertrophic myocardial cells].

OBJECTIVE: To study the effects of electroacupuncture (EA) at Neiguan (PC6) on c-Jun NH2-terminal kinases (JNK) signaling pathways in hypertrophic myocardial cells. METHODS: Thirty female SD rats were randomly divided into three groups, i.e., the normal group, the model group, and the EA group, 10 in each group. Isoprenaline hydrochloride (ISO) injection at the daily dose of 3 mg/kg was subcutaneously injected for 14 days to establish the cardiac hypertrophy (CH) model. Rats in normal group were subcutaneously injected with an equal volume of normal saline. EA at Neiguan (PC6) was applied for rats in the EA group while modeling, once daily, for 14 successive days. The left ventricular weight index (LVWI) and heart weight index (HWI) were calculated in all rats. The content of angiotensin II (Ang II) in the cardiac muscular tissue was tested using radioimmunoassay. The protein expressions of JNK and phosphorated JNK (p-JNK) in cardiocytes were detected using Western blot. RESULTS: Compared with the normal group, LVWI and HWI, the Ang II content, and the expressions of JNK and p-JNK were significantly higher in the model group, showing statistical difference (P < 0.01). The aforesaid indices were obviously lower in the EA group than in the model group with statistical difference (P < 0.05). CONCLUSIONS: EA at PC6 could prevent and treat CH possibly correlated with regulation of JNK signaling pathways. EA might play a role possibly through regulating its upstream neuroendocrine factors.

[Effects of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy].

OBJECTIVE: To discuss the mechanisms of electroacupuncture at "Neiguan" (PC 6) on p38 MAPK signaling pathway in rats with cardiac hypertrophy. METHODS: Forty SD rats were randomly divided into four groups: a normal group, a model group, a model plus p38 MAPK inhibitor group, a model plus electroacupuncture group, ten rats in each group. The model rats were established by subcutaneous injection 3 mg/(kg x d) of Isoprenaline Hydrochloride; model plus p38 MAPK inhibitor group were injected 0.3 mg/(kg x d) of specific inhibitor SB 203580; model plus electroacupuncture group was treated by electroacupuncture at "Neiguan"(PC 6) with continuous-wave, 2 Hz and 1 mA for 20 minutes, once a day for 14 days. There was no treatment in other two groups. The contents of TNF-alpha and IL-1beta in heart tissue were detected by radioimmunoassay and the p38 MAPK, p-p38 MAPK by western blot. RESULTS: Compared with normal group, the contents of TNF-alpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly increased in model group (all P < 0.01). The contents of TNFalpha, IL-1beta, p38 MAPK, p-p38 MAPK were significantly decreased in model plus p38 MAPK inhibitor group and model plus electroacupuncture group, compared with model group, all P < 0.05; compared with normal group, P < 0.05, P < 0.01; but no significant difference between model plus p38 MAPK inhibitor group and model plus electroacupuncture group (P > 0.05). CONCLUSION: Electroacupuncture at "Neiguan" (PC 6) can prevent the phosphorylation of p38 MAPK of myocardial hypertrophy, and the mechanism maybe adjust p38 MAPK signaling pathway by inhibiting the expression of TNF-alpha and IL-1beta.