Decreased colony formation of high proliferative potential colony-forming cells and granulocyte-macrophage colony-forming units and increased Hes-1 expression in bone marrow mononuclear cells from patients with psoriasis.
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.


OBJECTIVE
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.
Zhang
K
K
Institute of Dermatology, Taiyuan City Central Hospital, Affiliated with Shanxi Medical University, 1 Dong San Dao Xiang, Taiyuan 030009, Shanxi Province, China.
Hou
R
R
Niu
X
X
Zhang
J
J
Yin
G
G
Li
X
X
Jia
Y
Y
D000293:Adolescent; D000328:Adult; D000368:Aged; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D055014:Granulocyte-Macrophage Progenitor Cells / Q000378:metabolism / Q000473:pathology; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index; D019098:Telomerase / Q000378:metabolism; D000072056:Transcription Factor HES-1; D055815:Young Adult
D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D019098:Telomerase; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human