Abstract:This study aimed to reveal the mechanism of transcription factor Kruppel-like factor 4 (KLF4) in regulating M1 polarization of macrophages in rheumatoid arthritis (RA) in order to induce inflammatory response. The results suggested that KLF4 overexpression promoted the M1 polarization of RAW 264.7 cells, increased STAT1 expression and up-regulated the phosphorylation level. After KLF4 silencing, the M1 polarization level was down-regulated. Besides, the induced M1 macrophages were co-cultured with articular ch… Show more
“…However, the long-term chronic inflammatory response may lead to implant failure. During normal fracture healing, proinflammatory M1 macrophages gradually change to antiinflammatory M2 macrophages, a process that represents the resolution of inflammation and consequent osteogenic differentiation [23]. Therefore, timely regulation of macrophage transformation to the M2 phenotype and appropriate regulation of the inflammatory response is essential for the success of bone regeneration.…”
In bone tissue engineering, the bone immunomodulatory properties of biomaterials are critical for bone regeneration, which is a synergistic process involving physiological activities like immune response, osteogenesis, and angiogenesis. The effect of the macrophage immune microenvironment on the osteogenesis and angiogenesis of various material extracts was examined in this experiment using Mg2+ and Nano-hydroxyapatite/collagen (nHAC) in both a single application and a combined form. This study in vitro revealed that the two compounds combined significantly inhibited the NF-κB signaling pathway and reduced the release of inflammatory factors from macrophages when compared with the extraction phase alone. Additionally, by contributing to the polarization of macrophages towards the M2 type，the combined effects of the two materials can significantly improve osteogenesis/angiogenesis. The results of in vivo experiments confirmed that Mg2+/nHAC significantly promoted bone regeneration and angiogenesis. This study offers a promising method for enhancing bone graft material osseointegration.
“…However, the long-term chronic inflammatory response may lead to implant failure. During normal fracture healing, proinflammatory M1 macrophages gradually change to antiinflammatory M2 macrophages, a process that represents the resolution of inflammation and consequent osteogenic differentiation [23]. Therefore, timely regulation of macrophage transformation to the M2 phenotype and appropriate regulation of the inflammatory response is essential for the success of bone regeneration.…”
In bone tissue engineering, the bone immunomodulatory properties of biomaterials are critical for bone regeneration, which is a synergistic process involving physiological activities like immune response, osteogenesis, and angiogenesis. The effect of the macrophage immune microenvironment on the osteogenesis and angiogenesis of various material extracts was examined in this experiment using Mg2+ and Nano-hydroxyapatite/collagen (nHAC) in both a single application and a combined form. This study in vitro revealed that the two compounds combined significantly inhibited the NF-κB signaling pathway and reduced the release of inflammatory factors from macrophages when compared with the extraction phase alone. Additionally, by contributing to the polarization of macrophages towards the M2 type，the combined effects of the two materials can significantly improve osteogenesis/angiogenesis. The results of in vivo experiments confirmed that Mg2+/nHAC significantly promoted bone regeneration and angiogenesis. This study offers a promising method for enhancing bone graft material osseointegration.
“…The expression level of chemokine CCL7 was increased by P21 in our experiments, and CCL7 secreted by stressed epithelial cells in turn recruited macrophages via binding to CCR1/2/3 or CCR5/10 [ 50 , 51 ]. Meanwhile, infiltrated macrophages were polarized towards M1 phenotype, which would function as pro-inflammatory effects through the activation of NF-κB/STAT1 signaling pathways [ 52 , 53 ]. Fig.…”
Background
Interstitial lung diseases (ILDs) can be induced and even exacerbated by radiotherapy in thoracic cancer patients. The roles of immune responses underlying the development of these severe lung injuries are still obscure and need to be investigated.
Methods
A severe lung damage murine model was established by delivering 16 Gy X-rays to the chest of mice that had been pre-treated with bleomycin (BLM) and thus hold ILDs. Bioinformatic analyses were performed on the GEO datasets of radiation-induced lung injury (RILI) and BLM-induced pulmonary fibrosis (BIPF), and RNA-sequencing data of the severely damaged lung tissues. The screened differentially expressed genes (DEGs) were verified in lung epithelial cell lines by qRT-PCR assay. The injured lung tissue pathology was analyzed with H&E and Masson’s staining, and immunohistochemistry staining. The macrophage chemotaxis and activity promoted by the stressed epithelial cells were determined by using a cell co-culture system. The expressions of p21 in MLE-12 and Beas-2B cells were detected by qRT-PCR, western blot, and immunofluorescence. The concentration of CCL7 in cell supernatant was measured by ELISA assay. In some experiments, Beas-2B cells were transfected with p21-siRNA or CCL7-siRNA before irradiation and/or BLM treatment.
Results
After the treatment of irradiation and/or BLM, the inflammatory and immune responses, chemokine-mediated signaling pathways were steadily activated in the severely injured lung, and p21 was screened out by the bioinformatic analysis and further verified to be upregulated in both mouse and human lung epithelial cell lines. The expression of P21 was positively correlated with macrophage infiltration in the injured lung tissues. Co-culturing with stressed Beas-2B cells or its conditioned medium containing CCL7 protein, U937 macrophages were actively polarized to M1-phase and their migration ability was obviously increased along with the damage degree of Beas-2B cells. Furthermore, knockdown p21 reduced CCL7 expression in Beas-2B cells and then decreased the chemotaxis of co-cultured macrophages.
Conclusions
P21 promoted CCL7 release from the severely injured lung epithelial cell lines and contributed to the macrophage chemotaxis in vitro, which provides new insights for better understanding the inflammatory responses in lung injury.
Krüppel‐like factors (KLFs) are crucial in the development of bone disease. They are a family of zinc finger transcription factors that are unusual in containing three highly conserved zinc finger structural domains interacting with DNA. It has been discovered that it engages in various cell functions, including proliferation, apoptosis, autophagy, stemness, invasion and migration, and is crucial for the development of human tissues. In recent years, the role of KLFs in bone physiology and pathology has received adequate attention. In addition to regulating the normal growth and development of the musculoskeletal system, KLFs participate in the pathological process of the bones and joints and are intimately linked to several skeletal illnesses, such as osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP) and osteosarcoma (OS). Consequently, targeting KLFs has emerged as a promising therapeutic approach for an array of bone disorders. In this review, we summarize the current literature on the importance of KLFs in the emergence and regulation of bone illnesses, with a particular emphasis on the pertinent mechanisms by which KLFs regulate skeletal diseases. We also discuss the need for KLFs‐based medication‐targeted treatment. These endeavours offer new perspectives on the use of KLFs in bone disorders and provide prognostic biomarkers, therapeutic targets and possible drug candidates for bone diseases.
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