Background: Psoriasis is a chronic inflammatory disease of the skin. The dysfunctional immunity experienced by patients with psoriasis is believed to influence the bone marrow haematopoietic cells and their surrounding microenvironment. Phagocytes derived from the bone marrow of patients with active psoriasis exhibit enhanced monocytopoietic activity and hyperplasia in vitro. However, direct evidence supporting the hypothesis that bone marrow is involved in the pathogenesis of psoriasis has yet to be established.
Objectives: To investigate the involvement of bone marrow in the pathogenesis of psoriasis.
Methods: Bone marrow mononuclear cells (BMMNCs) were isolated from patients with psoriasis and healthy individuals. The high proliferative potential colony-forming cells (HPP-CFCs), granulocyte-macrophage colony-forming units (CFU-GM) and erythroid colony-forming units (CFU-E) were cultured in the presence of defined cytokines, and the effects of secreted factors from psoriatic peripheral blood mononuclear cells (PBMCs) on colony formation of normal haematopoietic cells were analysed. Furthermore, the telomere activity of psoriatic and normal BMMNCs was determined using the polymerase chain reaction (PCR)-based telomeric repeat amplification protocol, while the expression of human telomerase reverse transcriptase (hTERT) and HES1 mRNA was detected by reverse transcription-PCR assay.
Results: The numbers of HPP-CFCs and CFU-GM, but not CFU-E, were significantly reduced in cultured haematopoietic cells from patients with psoriasis. The culture supernatant of PBMCs from patients with psoriasis was found to inhibit the colony formation capacity of HPP-CFCs, CFU-GM and CFU-E of normal haematopoietic cells. We also detected low levels of telomerase activity and hTERT gene expression in psoriatic and control BMMNCs that was statistically similar between the two groups. In contrast, the HES1 gene expression appeared to be significantly elevated in psoriatic BMMNCs (P < 0.05).
Conclusions: Together, our results indicate the involvement of bone marrow in the immunopathogenesis of psoriasis, and suggest a mechanism mediated by certain inflammatory or haematopoietic cytokines present in the bone marrow microenvironment. Elevated expression levels of HES1 mRNA suggest a potential role for the Notch signalling pathway in this process.