K+ channel-blocking alkoxypsoralens inhibit the immune response of encephalitogenic T line cells and lymphocytes from Lewis rats challenged for experimental autoimmune encephalomyelitis

Ulf Strauss, Kirsten Wissel, Stefan Jung, Heike Wulff, Wolfram Hänsel, Jie Zhu, Arndt Rolfs, Eilhard Mix

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K+ channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K+ currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-γ (IFN-γ) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-γ gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K+ channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)51-63
Number of pages13
JournalImmunopharmacology
Volume48
Issue number1
DOIs
StatePublished - Jun 2000
Externally publishedYes

Fingerprint

Autoimmune Experimental Encephalomyelitis
Lymphocytes
Myelin Basic Protein
Methoxsalen
T-Lymphocytes
Cell Line
Interferons
Multiple Sclerosis
Autoimmune Diseases of the Nervous System
Lymph Nodes
Enzyme-Linked Immunosorbent Assay
4-Aminopyridine
Demyelinating Diseases
Patch-Clamp Techniques
Immunosuppressive Agents
Thymidine
Reverse Transcription
Immunization
Signal Transduction
Spinal Cord

Keywords

  • Alkoxypsoralens
  • Experimental autoimmune encephalomyelitis
  • Interferon-γ
  • K channels
  • Lymphocyte proliferation

ASJC Scopus subject areas

  • Pharmacology

Cite this

K+ channel-blocking alkoxypsoralens inhibit the immune response of encephalitogenic T line cells and lymphocytes from Lewis rats challenged for experimental autoimmune encephalomyelitis. / Strauss, Ulf; Wissel, Kirsten; Jung, Stefan; Wulff, Heike; Hänsel, Wolfram; Zhu, Jie; Rolfs, Arndt; Mix, Eilhard.

In: Immunopharmacology, Vol. 48, No. 1, 06.2000, p. 51-63.

Research output: Contribution to journalArticle

Strauss, Ulf ; Wissel, Kirsten ; Jung, Stefan ; Wulff, Heike ; Hänsel, Wolfram ; Zhu, Jie ; Rolfs, Arndt ; Mix, Eilhard. / K+ channel-blocking alkoxypsoralens inhibit the immune response of encephalitogenic T line cells and lymphocytes from Lewis rats challenged for experimental autoimmune encephalomyelitis. In: Immunopharmacology. 2000 ; Vol. 48, No. 1. pp. 51-63.
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abstract = "Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K+ channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K+ currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-γ (IFN-γ) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-γ gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K+ channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity. Copyright (C) 2000 Elsevier Science B.V.",
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AU - Wissel, Kirsten

AU - Jung, Stefan

AU - Wulff, Heike

AU - Hänsel, Wolfram

AU - Zhu, Jie

AU - Rolfs, Arndt

AU - Mix, Eilhard

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N2 - Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K+ channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K+ currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-γ (IFN-γ) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-γ gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K+ channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity. Copyright (C) 2000 Elsevier Science B.V.

AB - Alkoxypsoralens, known as DNA photomodifying agents, have been shown to block voltage-dependent K+ channels (Kv) as well as to alleviate functional deficits in certain multiple sclerosis (MS) patients in a manner similar to 4-aminopyridine. Since Kv channel blockers are known to inhibit T cell-mediated immune responses both in vitro and in vivo, we investigated the effects of three alkoxypsoralens, 5-methoxypsoralen (5-MOP), 8-methoxypsoralen (8-MOP), and 5,8-diethoxypsoralen (H37), on the following parameters: (1) whole-cell K+ currents of encephalitogenic, myelin basic protein-specific memory T cell line cells (MBP-TCLC) derived from Lewis rats as measured by patch-clamp technique, (2) proliferation of MBP-TCLC and lymph node cells (LNC) from Lewis rats challenged for experimental autoimmune encephalomyelitis (EAE) by immunisation with spinal cord homogenate as measured by 3H-thymidine incorporation, (3) interferon-γ (IFN-γ) secretion of MBP-TCLC as measured by ELISA, and (4) IFN-γ gene expression of LNC as measured by quantitative reverse transcription polymerase chain reaction (RT-PCR) with ELISA-detection. The examined alkoxypsoralens exhibited suppressive effects on the measured parameters with the same sequence of efficacy: H37>5-MOP>8-MOP. We, therefore, conclude that Kv channel-blocking alkoxypsoralens interfere with voltage-controlled signal transduction in lymphocytes and might thereby suppress immune responses in autoimmune diseases of the central nervous system and most likely also in other autoimmune disorders. Thus, alkoxypsoralens, especially the non-phototoxic substance H37, are new candidates for further studies on K+ channel blocking immunosuppressive drugs. The agents may exert a dual beneficial effect on demyelinating diseases like MS, because they could attenuate the inflammatory process and improve axonal conductivity. Copyright (C) 2000 Elsevier Science B.V.

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