Background/Aims: Histamine remains the main mediator of allergic conjunctivitis and induces interleukin (IL)-6 and IL-8 production in human conjunctival epithelial cells (HCEC). The purpose of the present study was to determine whether histamine induced IL-6 and IL-8 expression in HCEC, and to describe the relationship between human calcium-activated chloride channel (hCLCA) 1 activity and IL-6 and IL-8 expression. Methods: HCEC were isolated from human conjunctiva and cultured at an air-liquid interface. IL-6 and IL-8 mRNA expression was examined by real-time PCR, and IL-6 and IL-8 secretion was measured by ELISA after stimulation of HCEC with histamine. Results: Histamine upregulated IL-6 and IL-8 expression and IL-6 and IL-8 secretion in a dose-dependent manner in HCEC. Niflumic acid (NFA), an hCLCA blocker, reduced histamine-induced IL-6 and IL-8 expression. Conclusion: Histamine-induced IL-6 and IL-8 production could be attenuated by NFA, an hCLCA blocker.

1.
Woodward DF, Nieves AL, Spada CS, Williams LS, Tuckett RP: Characterization of a behavioral model for peripherally evoked itch suggests platelet-activating factor as a potent pruritogen. J Pharmacol Exp Ther 1995;272:758-765.
2.
Proud D, Sweet J, Stein P, Settipane RA, Kagey-Sobotka A, Friedlaender MH, Lichtenstein LM: Inflammatory mediator release on conjunctival provocation of allergic subjects with allergen. J Allergy Clin Immunol 1990;85:896-905.
3.
Dachman WD, Bedarida G, Blaschke TF, Hoffman BB: Histamine-induced venodilation in human beings involves both H1 and H2 receptor subtypes. J Allergy Clin Immunol 1994;93:606-614.
4.
Bielory L: Allergic and immunologic disorders of the eye. Part II. Ocular allergy. J Allergy Clin Immunol 2000;106:1019-1032.
5.
Leonardi A: Role of histamine in allergic conjunctivitis. Acta Ophthalmol Scand Suppl 2000;230:18-21.
6.
Sharif NA, Xu SX, Magnino PE, Pang IH: Human conjunctival epithelial cells express histamine-1 receptors coupled to phosphoinositide turnover and intracellular calcium mobilization: role in ocular allergic and inflammatory diseases. Exp Eye Res 1996;63:169-178.
7.
Leverkoehne I, Gruber AD: The murine mCLCA3 (alias gob-5) protein is located in the mucin granule membranes of intestinal, respiratory, and uterine goblet cells. J Histochem Cytochem 2002;50:829-838.
8.
Yanni JM, Weimer LK, Sharif NA, Xu SX, Gamache DA, Spellman JM: Inhibition of histamine-induced human conjunctival epithelial cell responses by ocular allergy drugs. Arch Ophthalmol 1999;117:643-647.
9.
Pauly A, Brignole-Baudouin F, Guenoun JM, Riancho L, Rat P, Warnet JM, Baudouin C: Comparative study of topical anti-allergic eye drops on human conjunctiva-derived cells: responses to histamine and IFNγ and toxicological profiles. Graefes Arch Clin Exp Ophthalmol 2007;245:534-546.
10.
Dunford PJ, O'Donnell N, Riley JP, Williams KN, Karlsson L, Thurmond RL: The histamine H4 receptor mediates allergic airway inflammation by regulating the activation of CD4+ T cells. J Immunol 2006;176:7062-7070.
11.
Doganci A, Eigenbrod T, Krug N, de Sanctis GT, Hausding M, Erpenbeck VJ, Haddadel B, Lehr HA, Schmitt E, Bopp T, Kallen KJ, Herz U, Schmitt S, Luft C, Hecht O, Hohlfeld JM, Ito H, Nishimoto N, Yoshizaki K, Kishimoto T, Rose-John S, Renz H, Neurath MF, Galle PR, Finotto S: The IL-6R α chain controls lung CD4+CD25+ Treg development and function during allergic airway inflammation in vivo. J Clin Invest 2005;115:313-325.
12.
Cromwell O, Hamid Q, Corrigan CJ, Barkans J, Meng Q, Collins PD, Kay AB: Expression and generation of interleukin-8, IL-6 and granulocyte-macrophage colony-stimulating factor by bronchial epithelial cells and enhancement by IL-1 beta and tumour necrosis factor-alpha. Immunology 1992;77:330-337.
13.
Miyoshi T, Fukagawa K, Shimmura S, Fujishima H, Takano Y, Takamura E, Tsubota K, Saito H, Oguchi Y: Interleukin-8 concentrations in conjunctival epithelium brush cytology samples correlate with neutrophil, eosinophil infiltration, and corneal damage. Cornea 2001;20:743-747.
14.
Wakefield D, Lloyd A: The role of cytokines in the pathogenesis of inflammatory eye disease. Cytokine 1992;4:1-5.
15.
Seo KY, Jeon S, Choi SH, Chung SH: Niflumic acid reduces histamine-induced MUC5AC expression in human conjunctival epithelial cells. Ophthalmic Res 2011;46:181-186.
16.
Chung SH, Lee JH, Yoon JH, Lee HK, Seo KY: Multi-layered culture of primary human conjunctival epithelial cells producing MUC5AC. Exp Eye Res 2007;85:226-233.
17.
Hegab AE, Sakamoto T, Nomura A, Ishii Y, Morishima Y, Iizuka T, Kiwamoto T, Matsuno Y, Homma S, Sekizawa K: Niflumic acid and AG-1478 reduce cigarette smoke-induced mucin synthesis: the role of hCLCA1. Chest 2007;131:1149-1156.
18.
Ang LP, Tan DT, Seah CJ, Beuerman RW: The use of human serum in supporting the in vitro and in vivo proliferation of human conjunctival epithelial cells. Br J Ophthalmol 2005;89:748-752.
19.
Barnett J, Chow J, Ives D, Chiou M, Mackenzie R, Osen E, Nguyen B, Tsing S, Bach C, Freire J, et al: Purification, characterization and selective inhibition of human prostaglandin G/H synthase 1 and 2 expressed in the baculovirus system. Biochim Biophys Acta 1994;1209:130-139.
20.
Hinson RM, Williams JA, Shacter E: Elevated interleukin 6 is induced by prostaglandin E2 in a murine model of inflammation: possible role of cyclooxygenase-2. Proc Natl Acad Sci USA 1996;93:4885-4890.
21.
Shacter E, Arzadon GK, Williams J: Elevation of interleukin-6 in response to a chronic inflammatory stimulus in mice: inhibition by indomethacin. Blood 1992;80:194-202.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.