Promoter methylation status of p15 and p21 genes in HPP-CFCs of bone marrow of patients with psoriasis

Psoriasis is an inflammatory disease related to dysfunctional immunity. The dysfunctional immunity may influence the haematopoietic microenvironment or haematopoiesis in psoriasis. However, direct evidence is lacking. Our objective was to investigate the proliferation of hematopoietic cells from psoriatic patients and any link between the promoter methylation status of p15 and p21 genes and the colony formation ability of high proliferative potential colony-forming cells (HPP-CFCs). Marrow mononuclear cells were isolated from the bone marrow of psoriatic patients and normal controls by density gradient centrifugalization. Colony forming assays of HPP-CFCs were performed in vitro in methylcellulose semi-solid culture medium. mRNA expression and the promoter methylation status of p15 and p21 genes in HPP-CFCs were studied by semi-quantitative RT-PCR and methylation-specific PCR respectively. In methycellulose semi-solid culture system, the colony count of HPP-CFCs in bone marrow of psoriatic patients was significantly less than that of normal controls. Moreover, significantly lower positive frequencies of promoter methylation and higher transcription levels for p15 and p21 genes were observed in psoriasis in comparison to normal volunteers. The lower promoter methylation of p15 and p21 genes may be an important mechanism for the dysfunctional growth regulation pathways in HPP-CFCs in psoriasis.