Induction of cyclooxygenase-1 in a human megakaryoblastic cell line (CMK) differentiated by phorbol ester

Ueda, Natsuo; Yamashita, Ryoko; Yamamoto, Shozo; Ishimura, Kazunori

doi:10.1016/s0005-2760(96)00131-2

Cited by 36 publications

(34 citation statements)

References 28 publications

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“…A COX mRNA isoform switch has never been quantitatively demonstrated before, although previous studies have documented such a switch without using quantitative methods (23). Accumulating evidence suggests that COX-1 expression can be modulated and expressed differentially by different cells under various conditions, including nerve cells and human brain injury, phorbol ester stimulation of THP-1 cells, phorbol ester (TPA [12-O-tetradecanoylphorbol-13-acetate]) stimulation of human megakaryoblastic-like cells, and tobacco carcinogen treatment of a human macrophage cell line (23)(24)(25). Another system in which LPS has been shown to differentially regulate constitutive and inducible transcription factor activity in rats includes the downregulation of DNA-binding activities of the constitutive transcription factors SP-1 and AP-2 (26).…”

Section: Discussionmentioning

confidence: 99%

Altered Monocyte Cyclooxygenase Response to Lipopolysaccharide in Type 1 Diabetes

Beyan¹,

Goodier²,

Nawroly³

et al. 2006

Diabetes

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Type 1 diabetes is caused by adaptive immune responses, but innate immunity is important because monocytes infiltrate islets. Activated monocytes express cyclooxygenase (COX)-2, promoting prostaglandin-E 2 (PGE 2 ) secretion, whereas COX-1 expression is constitutive. We aimed to define monocyte COX expression in type 1 diabetes basally and after lipopolysaccharide (LPS) stimulation. Isolated CD14 ؉ monocytes were analyzed for COX mRNA and protein expression from identical twins (discordant for type 1 diabetes) and control subjects. Basal monocyte COX mRNA, protein expression, and PGE 2 secretion were normal in type 1 diabetic subjects. After LPS, twins and control subjects showed a COX mRNA isoform switch with decreased COX-1 mRNA (P < 0.01), increased COX-2 mRNA (P < 0.01), and increased COX-2 protein expression (P < 0.01). Compared with control subjects, both diabetic and nondiabetic twins showed greater LPS-induced downregulation of monocyte COX-1 mRNA (P ‫؍‬ 0.02), reduced upregulation of COX-2 mRNA and protein (P < 0.03), and greater inhibition by the COX-2 inhibitor di-isopropylfluorophosphate (DFP) of monocyte PGE 2 (P < 0.007). We demonstrate an alteration in monocyte COX mRNA expression as well as monocyte COX-2 and PGE 2 production after LPS in type 1 diabetic patients and their nondiabetic twins. Because COX-2 response to LPS is proinflammatory, an inherited reduced response would predispose to chronic inflammatory diseases such as type 1 diabetes. Diabetes 55: 3439 -3445, 2006

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Section: Discussionmentioning

confidence: 99%

Altered Monocyte Cyclooxygenase Response to Lipopolysaccharide in Type 1 Diabetes

Beyan¹,

Goodier²,

Nawroly³

et al. 2006

Diabetes

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“…The cells differentiate to mature megakaryocyte-like cells by treatment with phorbol ester (TPA) or dimethyl sulfoxide (13,14). Recently we showed that cyclooxygenase-1, but not cyclooxygenase-2, was induced in CMK cells during the differentiation (15). The cyclooxygenase-1 is well known as a constitutive enzyme present in platelets (16,17), and is responsible for the production of proaggregatory thromboxane A 2 essentially as a sole cyclooxygenase metabolite.…”

Section: Prostaglandin (Pg)mentioning

confidence: 99%

“…The cyclooxygenase-1 is well known as a constitutive enzyme present in platelets (16,17), and is responsible for the production of proaggregatory thromboxane A 2 essentially as a sole cyclooxygenase metabolite. However, we found that the TPA-treated CMK cells produced PGD 2 as a major product in addition to thromboxane A 2 (15). Since PGD 2 was reported not to be produced in platelets (18), we were interested in the megakaryoblastic production of PGD 2 and attempted to characterize the responsible enzyme.…”

Section: Prostaglandin (Pg)mentioning

confidence: 99%

“…Other reagents used for Northern (15) and Western (19) blots were purchased as described previously. CMK cells were kindly provided by Dr. Eiji Shimizu of the Third Department of Internal Medicine, Tokushima University School of Medicine, with the consent of Dr. Takeyuki Sato of Chiba University, and Dami cells by Dr. Hiroshi Miyazaki of Kirin Brewery Company (Takasaki, Japan).…”

Section: Materials-[1-mentioning

confidence: 99%

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Prostaglandin D Synthase in Human Megakaryoblastic Cells

Mahmud

Ueda

Yamaguchi

et al. 1997

Journal of Biological Chemistry

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The cytosol fraction of human platelets did not convert prostaglandin (PG) H 2 to PGD 2 . However, a homogenate of human megakaryoblastic CMK cells (precursor cells of platelets) produced PGD 2 from PGH 2 . The PGD synthase activity was localized in the cytosol of CMK cells, and absolutely required glutathione. The catalytic properties and Western and Northern blottings indicated that the enzyme was PGD synthase of the hematopoietic type rather than the lipocalin type. When CMK cells were differentiated to megakaryocytes with phorbol ester along with induction of cyclooxygenase-1, the PGD synthase activity increased about 2-fold for 2 days and then decreased. In another human megakaryoblastic cell line, Dami, the PGD synthase increased about 10-fold by the addition of phorbol ester. Thus, the PGD synthase, which was undetectable in platelets, appeared during differentiation of megakaryoblasts to megakaryocytes.

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“…A concentração da COX-1, normalmente, é constante. Contudo, pequenos aumentos podem ocorrer em resposta a estímulos por hormônios ou fatores de crescimento (DEWITT, 1991;UEDA et al, 1997). A expressão constitutiva da COX-2 ocorre em algumas áreas do sistema nervoso central (YAMAGATA et al, 1993;BREDER et al, 1995;CAO et al, 1995), em tecidos envolvidos na reprodução, além de rins e timo (SMITH e LANGENBACH, 2001) e no sistema gástrico (KARGMAN et al, 1996).…”

Section: Eicosanóidesunclassified

Caracterização da reação inflamatória induzida pelo veneno da serpente Bothrops insularis: Influxo leucocitário, liberação de mediadores inflamatórios e mecanismos envolvidos nesses efeitos

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Induction of cyclooxygenase-1 in a human megakaryoblastic cell line (CMK) differentiated by phorbol ester

Cited by 36 publications

References 28 publications

Altered Monocyte Cyclooxygenase Response to Lipopolysaccharide in Type 1 Diabetes

Altered Monocyte Cyclooxygenase Response to Lipopolysaccharide in Type 1 Diabetes

Prostaglandin D Synthase in Human Megakaryoblastic Cells

Caracterização da reação inflamatória induzida pelo veneno da serpente Bothrops insularis: Influxo leucocitário, liberação de mediadores inflamatórios e mecanismos envolvidos nesses efeitos

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