CPB 697 RESEARCH SEMINAR
William D. Follas, MS
Graduate Student in Clinical Pathology
Department of Comparative Pathobiology
“Porcine Macrophage Adiponectin Receptors, AdipoR1 And AdipoR2,
And Cytokines TNFα,
TGFβ And IL-10
Expression Are Modulated By in vitro
LPS Stimulation”
Thursday, April 26, 2007
VPTH 112
3:30 pm
Abstract:
Macrophages are derived from the pluripotent stem cell through the myeloid lineage in the hematopoietic process. The immediate progenitor cell for the peripheral blood derived macrophage is the monocyte which is found in the peripheral circulation. Isolation and subsequent maturation of cultured peripheral blood derived porcine macrophages was assessed through the use of monocyte (SWC-1) and macrophage (SWC-9) specific cell surface antigen markers.
Adiponectin, a 244 amino acid protein, has demonstrated insulin sensitizing effects as well as anti-atherogenic properties. It has been shown to cause decreases in the production of the pro-inflammatory cytokines TNF-α and IL-6 in porcine macrophages while eliciting an increase in the anti-inflammatory cytokine IL-10. Additionally, adiponectin decreases the LPS induced phagocytic response in the macrophage while inhibiting the proliferation of myelomonocytic cells.
Adiponectin has two receptors designated as AdipoR1 and AdipoR2. These receptors are expressed in varying concentrations in most tissues including brain, heart, kidney, liver, lung, skeletal muscle, spleen and testis tissues. An example of the relative receptor concentrations in tissues is seen in mice where AdipoR1 is predominant in skeletal muscle while AdipoR2 is predominant in liver with varying concentrations in the other tissues. Additionally, human adipose tissue in obese individuals exhibits decreased AdipoR1 while placental biopsies from gestational DM patients have increased AdipoR1. Interestingly, it has also been shown that AdipoR1/R2 concentrations can be modulated under differing conditions such as that in which TNFα decreases AdipoR2 in stromal vascular cells of the pig.
Taken together, it is believed that the inflammatory state caused by an LPS challenge of the porcine macrophage will cause a change in the adiponectin receptors’ expression. Our preliminary experiments have shown down regulation of AdipoR1, AdipoR2, TGFβ and up regulation of TNFα and IL-10 in LPS stimulated PDBM macrophages as measured by RT-PCR.