Dexamethasone Modulates IL-13 and IL-10 Expression

Abstract

Interleukin (IL-)-10 and IL-13 are Th2-cell-associated cytokines with a variety of biologic activities in immune and inflammatory responses. It is known that glucocorticoids (GCs) modulate inflammatory and immune functions. In fact, GCs are involved to regulate the transcription of cytokines which are relevant in chronic inflammation and cell-mediated immune response.

In the present study we analyzed, in vitro, the effects of DEX on the expression of the IL-10 and IL-13 lymphokines in murine spleen and thymus cells. DEX-stimulation induced down-regulation of the expression of IL-10 and IL-13 mRNA.

This effect was already evident 0.5 hr after treatment and persisted in time, in both resting and activated lymphocytes. These results suggest that GCs could have inhibitory effect on Th2 cytokine production.

Keywords

DEX IL-10 IL-13 T lymphocytes

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References

Beato

1989. Gene regulation by steroid hormones. Cell 56: 335.

Barnes

P.J.

and Adcock

. 1993. Anti-inflammatory actions of steroids: molecular mechanism TiPS. 14: 436.

Willie

A. H.

1980. Glucocorticoid-induced thtmocyte apoptosis is associated with endogenous activation. Nature 284:555.

Williams

C.M.M.

and Coleman

J.W.

. 1995. Induced expression of mRNA for IL-5, IL-6, TNFa, MIP-2 and IFN-g in immunologically activated rat peritoneal mast cells: inhibition by dexamethasone and cyclosporin A. Immunology, 86, 244.

Kern

J.A.

Lamb

R.J.

Reed

J.C.

Danielle

R.P.

and Nowell

P.C.

. 1988. Dexamethasone inibition of interleukin-b production by human monocytes: post-transcriptional mechanisms. J. Clin. Invest. 81: 237.

Von Kuebel Doeberitz

Koch

Drzonek

and Zur Hansen

. 1990. Glucocorticoid hormones reduce the expression of major histocompatibility class I antigens on human epithelia cells. Eur. J. Immunol. 20: 35.

Muzio

De Rossi

Polentarutti

Giri

J. G.

Mantovani

and Colotta

. 1994. The type II “Receptor” as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor. J. Exp. Med. 179: 739.

Auphan

DiDonato

J.A.

Rosette

Helmberg

and Karin

. 1995. Immunosuppression by glucocorticoids: inhibition of NF-kB activity through induction of IkB synthesis. Science 270:286.

Lew

Oppenheim

J.J.

and Matsushima

. 1988. Analysis of suppression of IL-1a and IL-b production in human peripheral blood mononuclear adherent cells by a glucocorticoid hormone. J. Immunol. 140: 1895.

10.

Han

Thompson

and Beutler

. 1990. Dexamethasone and pentoxifylline inhibit endotoxic-induced cachectin/tumor necrosis factor synthesis at separate points in the signaling pathway. J. Exp. Med. 172:391.

11.

Waage

Slupphaug

and Shalaby

. 1990. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur. J. Immunol. 20: 2439.

12.

Strieter

R.M.

Standiford

T.J.

Rolfe

M.W.

and Kunkel

S.L.

. 1993. Interleukin-8. In Cytokines of the Lung. Kelly and Dekker, New York, p. 281.

13.

Ramirez

Fowell

D.J.

Puclavec

Simmonds

and Mason

. 1996. Glucocorticoids promote a Th2 cytokine response by CD4⁺ T cells in vitro. J. Immunol. 156: 2406.

14.

Krouwels

F.H.

van der Heijden

J.F.

Lutter

van Neerven

R.J.

Jansen

H.M.

and Out

T.A.

1997. Glucocorticosteroids affect functions of airway-and blood-derived human T-cell clones, favoring the Th1 profile through two mechanism. Am. J. Respir. Cell. Mol. Biol. 14: 388.

15.

Enk

A.H.

and Katz

S.I.

. 1992. Identification and induction of keratinocytes-derived IL-10. J. Immunol. 149:92.

16.

Moore

K.W.

O'Garra

de Waal Malefyt

Vieira

and Mosmann

T.R.

. 1993. Interleukin 10. Annu. Rev. Immunol. 11: 165.

17.

de Waal Malefyt

Abrams

Bennet

Figdor

and de Vries

. 1991. IL-10 inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 174: 1209.

18.

de Waal Malefyt

Haanen

Spits

Roncarolo

M.G.

de Velde

Fidgor

Johnson

Kastelein

Yssel

and de Vries

J.E.

. 1991. IL-10 and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminuishing the antigen-presenting capacity of monocytes via downregulation of class II MHC expression. J. Exp. Med. 174: 915.

19.

Fiorentino

D.F.

Zlotnik

Mosmann

T.R.

Howard

M.H.

and O'Garra

. 1991. IL-10 inhibts cytokine production by activated macrophages. J. Immunol. 147: 3815.

20.

Bodgan

Vodovotz

and Nathan

. 1991. Macrophage deactivation by interleukin 10. J. Exp. Med. 174: 1549.

21.

N.F.

Castle

B.E.

Barret

Kastelein

Dang

Mosmann

T.R.

Moore

K.W.

and Howard

. 1990. Interleukin 10 (IL-10), a novel B cell stimulatory factor: unresponsiveness of X chromosome-linked immunodeficiency B cells. J. Exp. Med. 172: 1625.

22.

Rousset

Garcia

Defrance

Peronne

Hsu

D.H.

Kastelein

Moore

K. W.

and Banchereau

. 1992. IL-10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc. Natl. Acad. Sci. USA. 89: 1890.

23.

MacNeil

I.A.

Suda

Moore

K.W.

Mosmann

T.R.

and Zlotnik

. 1990. IL-10, a novel growth factor for mature and immature T cells. J. Immunol. 145: 4167.

24.

Fiorentino

D.F.

Zlotnik

Vieira

Mosmann

T.R.

Howard

Moore

K.W.

and O'Garra

. 1991. IL-10 acts on the antigen presenting cell to inhibit cytokine production by Th1 cells. J. Immunol. 146: 3444.

25.

Cherwinski

H.M.

Schumacher

J.M.

Brown

K.D.

and Mosmann

T.R.

. 1987. Two types of mouse helper T cell clone. III. Further differences in lymphokine synthesis between Th1 and Th2 clones revealed by RNA hybridization, functionally monospecific bioasays, and monoclonal antibodies. J. Exp. Med. 166: 1229.

26.

Brown

K.D.

Zurawski

S.M.

Mosmann

T.R.

and Zurawski

. 1989. A family of small inducible proteins secreted by leukocytes are members of new superfamily that includes leukocytes and fibroblast-derived inflammatory agents, growth factors, and indicators of various activation processes. J. Immunol. 142: 679.

27.

Mc Kienzie

A.N.J.

Culpepper

J. A.

de Waal Malefyt

Briere

Punnonen

Aversa

Sato

Dang

Cocks

B.G.

Menon

de Vries

J.E.

Banchereau

and Zurawski

. 1992. Interleukin-13, a novel T cell-derived cytokine that regulates human monocyte and B cell function. Proc. Natl. Acad. Sci. USA. 90: 3735.

28.

Minty

Chalon

Derocq

J.M.

Dumont

Guillemot

J.C.

Kaghad

Labit

Leplatois

Liauzun

Miloux

Minty

Casellas

Loison

Lupker

Shire

Ferrara

and Caput

. 1993. Interleukin-13 is a new human lymphokine regulating inflammatory and immune responses. Nature 362: 248.

29.

Zurawski

and de Vries

J.E.

. 1994. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol. Today 15: 19.

30.

Doherty

T.M.

Kastelein

Menon

Andrade

and Cofman

R.L.

. 1993. Modulation of murine macrophage function by IL-13. J. Immunol. 150: 7151.

31.

Montaner

L.J.

Doyle

A.G.

Collin

Herbein

Illei

Minty

Caput

Ferrara

and Gordon

. 1993. Interleukin 13 inhibts human immunodeficiency virus type I production in primary blood-derived human macrophages in vitro. J. Exp. Med. 178: 743.

32.

Punnonen

Aversa

Cocks

B.G.

McKenzie

A.N.J.

Menon

Zurawski

de Waal Malefyt

and de Vries

J.E.

1993. Interleukin 13 induces interleukin 4-independent IgG4 and IgE synthesis and CD23 expression by human B cells. Proc. Natl. Acad. Sci. USA 90: 3730.

33.

Fiorentino

D. F.

Bond

M.A.

and Mosmann

T.R.

. 1989. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J. Exp. Med. 170: 2081.

34.

Hopkins

and Humphreys

. 1989. Simple, sensitive and specific bioassay of interleukin-1. J. Immun. Meth. 120: 271.

35.

Nicoletti

Migliorati

Pagliacci

M.C.

Grignani

and Riccardi

. 1991. A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry. J. Immun. Meth. 139: 271.

36.

Cohen

J.J.

and Duke

R.C.

. 1984. Glucocorticoid activation of a calcium dependent endonuclease in thymocyte nucleic leads to cell death. J. Immunol. 13: 38.

37.

Broski

A.P.

and Halloran

P.F.

. 1994. Tissue distribution of IL-10 mRNA in normal mice. Evidence that a component of IL-10 expression is T and B cell-independent and increased by irradiation. Transplantation. 57: 4.

38.

Tomkins

P.T.

Cooper

L.K.

Appleby

and Webber

D.G.

. 1995. Effect of pharmacological agents on the production of interleukin-10 by the murine D10.G4.1 Th2 cell line in vitro. Int. J. Immunopharmac. 17:619.

39.

Marietta

E.V.

Chen

and Weis

J.H.

. 1996. Modulation of expression of the anti-inflammatory cytokines interleukin-13 and interleukin-10 by interleukin-3. Eur. J. Immunol. 26: 4956.

40.

Schmidt

T.J.

and Davidson

C.J.

. 1987. The antiglucocorticoid, Cortexolone, fails to promote in vitro activation of cytoplasmic glucocorticoid receptors from the human leukemic cell line CEM-C7. J. Steroid Biochem. 26: 329.

41.

Zacharchuk

C.M.

Mercep

Chakraborti

P.K.

Simons

S.S.

Ashwell

J.R.

and Ashwell

J.D.

. 1990. Programmed T lymphocyte death. Cell activation-and steroid-induced pathways are mutually antagonistic. J. Immunol. 145: 4037.

42.

Sander

Hoidén

Andersson

Móller

and Abrams

J.S.

. 1993. Similar frequencies and kinetics of cytokine producing cells in murine peripheral blood and spleen. Cytokine detection by immunoassay and intracellular immunostaining. J. Immunol. Meth. 166: 201.

43.

Daynes

R.A.

and Araneo

B.A.

. 1989. Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4. Eur. J. Immunol. 19: 2319.

44.

Daynes

R.A.

Araneo

B.A.

Dowell

T.A.

Huang

and Dudley

. 1990. Regulation of murine lymphokine production in vivo. III. The lymphoid tissue microenvironment exerts regulatory influences over T helper cell function. J. Exp. Med. 171: 979.

45.

C.Y.

Fargeas

Nakajima

and Delespesse

. 1991. Glucocorticoids suppres the production of interleukin 4 by human lymphocytes. Eur. J. Immunol. 21: 2645.

46.

Byron

K.A.

Varigos

and Wootton

. 1992. Hydrocortisone inhibition of human interleukin-4. Immunol. 77: 624.