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Selective induction of PDGF gene expression in peritoneal macrophages by interleukin-2
E J Kovacs1, S Van Stedum, J E Neuman
1Department of Cell Biology, Neurobiology and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL.
Abstract:
We have previously reported that culture of human peripheral blood leukocytes with interleukin-2 (IL-2) triggers the secretion of mediators which induce fibroblast proliferation and collagen synthesis. In addition, fibrogenic cytokines (transforming growth factor-beta 1 (TGF beta 1) and platelet-derived growth factor (PDGF) A and B chain) are present in the peritoneal fluid of patients undergoing intraperitoneal immunotherapy (IL-2-activated killer cells and IL-2) who go on to develop peritoneal adhesions. To determine the role of IL-2 in the formation of these adhesions, we chose to investigate whether IL-2 can induce the expression of fibrogenic cytokine genes in resident rat peritoneal macrophages. Cells were cultured with or without IL-2 or lipopolysaccharide (LPS) and expression of PDGF A chain, PDGF B chain, and TGF beta 1 mRNAs was determined. PDGF A and B chain mRNAs are minimally expressed in macrophages prior to stimulation and are induced within 2 hours of treatment with IL-2. In contrast, TGF beta 1 mRNA is constitutively expressed and can not be upregulated. The studies suggest that peritoneal macrophage-derived PDGF plays a critical role in the production of adhesions in patients receiving intra-abdominal immunotherapy.
Insights
Interleukin-2 (IL-2) immunotherapy can cause peritoneal adhesions by stimulating macrophages to produce platelet-derived growth factor (PDGF). This study shows IL-2 induces PDGF gene expression in rat macrophages, a key factor in adhesion formation.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-2 (IL-2) immunotherapy is associated with peritoneal adhesions.
- Fibrogenic cytokines like transforming growth factor-beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are implicated in adhesion formation.
Purpose of the Study:
- To investigate the role of IL-2 in inducing fibrogenic cytokine gene expression in rat peritoneal macrophages.
- To determine if IL-2 can upregulate PDGF and TGF-β1 mRNA in macrophages.
Main Methods:
- Rat peritoneal macrophages were cultured with or without IL-2 or lipopolysaccharide (LPS).
- Expression of PDGF A chain, PDGF B chain, and TGF-β1 messenger RNAs (mRNAs) was quantified using molecular techniques.
Main Results:
- PDGF A and B chain mRNAs, minimally expressed in unstimulated macrophages, were significantly induced within 2 hours of IL-2 treatment.
- TGF-β1 mRNA was constitutively expressed and not upregulated by IL-2 stimulation.
Conclusions:
- IL-2 induces the expression of PDGF genes in peritoneal macrophages.
- Macrophage-derived PDGF likely plays a critical role in the development of peritoneal adhesions following intra-abdominal immunotherapy.