BAMBI promotes macrophage proliferation and differentiation in gliomas

Mol Med Rep. 2018 Mar;17(3):3960-3966. doi: 10.3892/mmr.2017.8320. Epub 2017 Dec 20.

Abstract

The present study investigated the capacity of Bone morphogenic protein and activin membrane‑bound inhibitor homolog (BAMBI) to regulate the migration and differentiation of macrophages in gliomas. Using a migration assay, it was determined that BAMBI stimulated monocytes migration in a dose‑dependent effect. When induced by phorbol myristate acetate (PMA) the monocytes differentiated into macrophages, and BAMBI also increased the migration of PMA‑induced macrophages compared with control cells. The expression of CD68 and BAMBI protein and mRNA in glioma and normal specimens were detected using immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction, respectively. The localization of BAMBI was primarily in macrophages, as demonstrated by staining for the macrophage marker CD68, and the mRNA expression of CD68 and BAMBI were higher in gliomas compared to normal tissues. In addition, the mRNA expression of CD68 and BAMBI were positively correlated (R2=0.64). After treatment with 50 nM PMA and 10 nM BAMBI for 48 h, RAW 264.7 macrophages were exhibited dendrite‑like morphology, indicating that the co‑treatment promoted the differentiation of monocytes to macrophages. The expression of specific markers of M1 [inducible nitric oxide synthase (iNOS) and interleukin (IL)-12] and M2 (IL-10 and arginase 1) type macrophages was determined following 10 nM BAMBI treatment. BAMBI promoted the expression of M1 markers, whereas the M2 markers were not affected, which indicated that BAMBI induced differentiation of M1 type macrophages. These results indicate that BAMBI may be involved in macrophage differentiation in gliomas.

Keywords: BAMBI; macrophage; gliomas; iNOS; IL-12.

MeSH terms

  • Adult
  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Arginase / genetics
  • Arginase / metabolism
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / genetics*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Membrane Proteins / pharmacology
  • Mice
  • Middle Aged
  • Neoplasm Grading
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • RAW 264.7 Cells
  • Signal Transduction
  • THP-1 Cells
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • BAMBI protein, human
  • CD68 antigen, human
  • IL10 protein, human
  • Membrane Proteins
  • Interleukin-10
  • Interleukin-12
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • ARG1 protein, human
  • Arginase
  • Tetradecanoylphorbol Acetate