Selected azaphenothiazines inhibit delayed type hypersensitivity and carrageenan reaction in mice

Artym, Jolanta; Kochanowska, Iwona; Kocięba, Maja; Zaczyńska, Ewa; Zimecki, Michał; Jeleń, Małgorzata; Morak‐Młodawska, Beata; Pluta, Krystian

doi:10.1016/j.intimp.2016.09.005

Cited by 10 publications

(10 citation statements)

References 18 publications

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“…Hitherto, our studies have shown that the azaphenothiazine derivative, DQT, exerts an immunosuppressive effect in in vivo models of delayed-type hypersensitivity to ovalbumin, carrageenan-induced footpad inflammation [9] and contact sensitivity to oxazolone [10]. More recently, we have shown that DQT can act by inhibiting the production of TNF-α, IL-8 and CXCL10 by describing its in vivo anti-psoriatic activity and potential feasibility in therapy [11].…”

Section: Discussionmentioning

confidence: 98%

“…Some of these compounds significantly inhibited mitogen-induced proliferation of human peripheral blood mononuclear cells, tumor necrosis factor alpha (TNFα) production in human whole blood cultures and the growth of tumor cell lines. Recent studies have also shown that newly synthesized azaphenothiazine derivatives exerted suppressive activity in in vivo models of: delayed-type hypersensitivity to ovalbumin and cutaneous carrageenan reaction [9], contact sensitivity to oxazolone [10] and experimental psoriasis in mice [11].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we studied anti-inflammatory activity of DQT in normal human keratinocytes to find a mechanism of CXCL10 expression inhibition by DQT. This may be important because this recently synthesized azaphenothiazine derivative may serve as a novel inhibitor of CXCL10 chemokine secretion with potential efficacy in therapy of autoimmunological diseases [4,[9][10][11] 2. Results…”

Section: Introductionmentioning

confidence: 99%

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An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

Strządała

Fiedorowicz

Wysokińska

et al. 2018

Preprint

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An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2’,3’-e][1,4]thiazine (DQT) has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB were not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C) as well as in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4-8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in pathogenesis of autoimmune diseases.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

Strządała

Fiedorowicz

Wysokińska

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Some of these compounds significantly inhibited mitogen-induced proliferation of human peripheral blood mononuclear cells, tumor necrosis factor alpha (TNFα) production in human whole blood cultures and the growth of tumor cell lines. Recent studies have also shown that newly synthesized azaphenothiazine derivatives exerted suppressive activity in in vivo models of: delayed-type hypersensitivity to ovalbumin and cutaneous carrageenan reaction [ 9 ], contact sensitivity to oxazolone [ 10 ] and experimental psoriasis in mice [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, we studied the anti-inflammatory activity of DQT in normal human keratinocytes to find the mechanism of CXCL10 expression inhibition by DQT. This may be important because this recently synthesized azaphenothiazine derivative may serve as a novel inhibitor of CXCL10 chemokine secretion with potential efficacy in therapy of autoimmunological diseases [ 4 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

et al. 2018

Self Cite

View full text Add to dashboard Cite

An azaphenothiazine derivative, 6-chloroethylureidoethyldiquino[3,2-b;2′,3′-e][1,4]thiazine (DQT), has recently been shown to exhibit immunosuppressive activities in mouse models. It also inhibited the expression of CXCL10 at the protein level, at non-toxic concentrations, in the culture of KERTr cells treated with double-stranded RNA, poly(I:C). In this report, we demonstrated that DQT inhibits the transcription of the CXCL10 gene. Although CXCL10 is an IFNγ-inducible protein, we found that the CXCL10 protein was induced without the detectable release of IFNγ or IκB degradation. Hence, we concluded that IFNγ or NFκB was not involved in the regulation of the CXCL10 gene in KERTr cells transfected with poly(I:C), nor in the inhibitory activity of DQT. On the other hand, we found that IFNβ was induced under the same conditions and that its expression was inhibited by DQT. Kinetic analysis showed that an increase in IFNβ concentrations occurred 4–8 h after poly(I:C) treatment, while the concentration of CXCL10 was undetectable at that time and started to increase later, when IFNβ reached high levels. Therefore, DQT may be regarded as a new promising inhibitor of IFNβ expression and IFNβ-dependent downstream genes and proteins, e.g., CXCL10 chemokine, which is implicated in the pathogenesis of autoimmune diseases.

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Evaluation of angularly condensed diquinothiazines as potential anticancer agents

Jeleń

Pluta

Latocha

et al. 2019

Bioorganic Chemistry

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Selected azaphenothiazines inhibit delayed type hypersensitivity and carrageenan reaction in mice

Cited by 10 publications

References 18 publications

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

Evaluation of angularly condensed diquinothiazines as potential anticancer agents

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Selected azaphenothiazines inhibit delayed type hypersensitivity and carrageenan reaction in mice

Cited by 10 publications

References 18 publications

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon &beta; Expression and CXCL10 Production in KERTr&nbsp;Cells

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon &beta; Expression and CXCL10 Production in KERTr&nbsp;Cells

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

Evaluation of angularly condensed diquinothiazines as potential anticancer agents

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Product

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An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells

An Anti-Inflammatory Azaphenothiazine Inhibits Interferon β Expression and CXCL10 Production in KERTr Cells