MicroRNA‐125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age

Abstract

Chemokines play a pivotal role in regulating the immune response through a tightly controlled expression. Elevated levels of inflammatory chemokines commonly occur with aging but the mechanism underlying this age-associated change is not fully understood. Here, we report the role of microRNA-125b (miR-125b) in regulating inflammatory CC chemokine 4 (CCL4) expression in human immune cells and its altered expression with aging. We first analyzed the mRNA level of CCL4 in eight different types of immune cells including CD4 and CD8 T-cell subsets (naïve, central and effector memory), B cells and monocytes in blood from both young (≤42 years) and old (≥70 years) adults. We observed that monocytes and naïve CD8 T cells expressed higher levels of CCL4 and exhibited an age-related increase in CCL4. We then found the level of miR-125b was inversely correlated with the level of CCL4 in these cells, and the level of miR-125b was reduced in monocytes and naïve CD8 T cells of the old compared to the young adults. Knock-down of miR-125b by shRNA in monocytes and naïve CD8 T cells led to an increase of CCL4 protein, whereas enhanced miR-125b expression by transfection in naïve CD8 T cells resulted in a reduction of the CCL4 mRNA and protein in response to stimulation. Finally, we demonstrated that miR-125b action requires the ‘seed’ sequence in 3′UTR of CCL4. Together these findings demonstrated that miR-125b is a negative regulator of CCL4 and its reduction is partially responsible for the age-related increase of CCL4.

Human omental adipose‐derived stem cells from donors with different body mass index had similar effects on proliferation and migration of endometrial cancer cells in vitro

“…In the current study, the expression of MIP‐1β secreted by O‐ASC was 21.14‐fold higher in the obesity group than in the normal group ( P = 0.03). However, the patients in the obesity group were relatively younger than the normal group which was not consistent with the previous reports . So, age may not be the single influence factor for the expression of MIP‐1β.…”

MiR‐126 correlates with increased disease severity and promotes keratinocytes proliferation and inflammation while suppresses cells' apoptosis in psoriasis

“…However, the molecular mechanisms behind these processes are still not fully understood. As regulatory elements, miRNAs play critical roles in immune diseases including psoriasis via participating in the development of immune cells, maintaining immune homeostasis, regulating innate and adaptive immunity, as well as regulating inflammatory factors …”

“…*P < .01, ***P < .001. HaCaT, human keratinocytes; NC, negative control elements, miRNAs play critical roles in immune diseases including psoriasis via participating in the development of immune cells, maintaining immune homeostasis, regulating innate and adaptive immunity, as well as regulating inflammatory factors [21][22][23][24].…”

Infiltrating T cells promote renal cell carcinoma (RCC) progressionviaaltering the estrogen receptor β-DAB2IP signals

“…Interestingly, although CCL4 expression did not change in RCC cells or T cells after co-culture, knocking down ERβ in 786-O cells and then co-culturing with T cells can lead to an increased CCL4 expression in the T cells. It has been known that the miR-125b can down-regulate CCL4 expression in monocytes and T cells by binding of the 3′UTR of CCL4 [ 54 ]. Meanwhile, activating transcription factor 3 (ATF3) also was found to repress the expression of CCL4 in murine macrophages [ 55 ].…”