Article tools
Author information
Published in Volume 100, Issue 10 (November 15,1997)
J. Clin. Invest. 100(10): 2443-2448 (1997). doi:10.1172/JCI119786.
Copyright © 1997, The American Society for Clinical Investigation.

Research Article

In vivo suppression of NF-kappa B and preservation of I kappa B alpha by interleukin-10 and interleukin-13.

A B Lentsch, T P Shanley, V Sarma and P A Ward

Department of Pathology, University of Michigan Medical School, Ann Arbor 48109, USA.

Published November 15, 1997

IL-10 and IL-13 have powerful antiinflammatory activities in vitro and in vivo. In the IgG immune complex model of lung injury in rats, exogenously administered IL-10 or IL-13 have recently been shown to suppress neutrophil recruitment and ensuing lung injury by greatly depressing pulmonary production of TNF alpha. Transcriptional control of the TNF alpha gene is regulated by the nuclear factor kappa B (NF-kappa B). Activation of NF-kappa B involves the degradation of its cytoplasmic inhibitor I kappa B alpha, allowing the nuclear translocation of NF-kappa B, with ensuing transcriptional activation. In this study, we sought to determine whether the protective effects of IL-10 and IL-13 in IgG immune complex-induced lung injury were mediated by inhibition of NF-kappa B activation. Electrophoretic mobility shift analysis of nuclear extracts from alveolar macrophages and whole lung tissues demonstrated that both IL-10 and IL-13 suppressed nuclear localization of NF-kappa B after in vivo deposition of IgG immune complexes. Western blot analysis indicated that these effects were due to preserved protein expression of I kappa B alpha in both alveolar macrophages and whole lungs. Northern blot analysis of lung mRNA showed that, in the presence of IgG immune complexes, IL-10 and IL-13 augmented I kappa B alpha mRNA expression. These findings suggest that in vivo, IL-10 and IL-13 may operate by suppressing NF-kappa B activation through preservation of I kappa B alpha.

This article Copyright © 1997, The American Society for Clinical Investigation.

Articles that cite
this article:

Systemic Inflammation-Associated Glucocorticoid Resistance and Outcome of ARDS
G UMBERTO Meduri, CHARLES R. Yates
Ann N Y Acad Sci 1024(1):24. [CrossRef]

IL-13 stimulates vascular endothelial cell growth factor and protects against hyperoxic acute lung injury
Jonathan Corne, Geoffrey Chupp, Chun Guen Lee, Robert J. Homer, Zhou Zhu, Qingsheng Chen, Bing Ma, Yuefen Du, Francoise Roux, John Mcardle
J Clin Invest 106(6):783. [CrossRef]

Chronic Inflammation in the Cystic Fibrosis Lung: Alterations in Inter- and Intracellular Signaling
David Nichols, James Chmiel, Melvin Berger
CRIAI 34(2):146. [CrossRef]

CD4+CD25+Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages
M. M. Tiemessen, A. L. Jagger, H. G. Evans, M. J. C. Van herwijnen, S. John, L. S. Taams
Proc Natl Acad Sci 104(49):19446. [CrossRef]

STAT3 and suppressor of cytokine signaling 3: potential targets in lung inflammatory responses
Hongwei Gao, Peter A Ward
eott 11(7):869. [CrossRef]

Cytokines in inflammatory diseases: role and therapeutic targets in acute respiratory distress syndrome
Thomas P Shanley
eott 2(2):1. [CrossRef]

In vivo B1 kinin-receptor upregulation. Evidence for involvement of protein kinases and nuclear factor κB pathways
Maria M Campos, Glória E P Souza, João B Calixto
Br J Pharmacol 127(8):1851. [CrossRef]

Anti-inflammatory Therapies for Cystic Fibrosis-Related Lung Disease
David P. Nichols, Michael W. Konstan, James F. Chmiel
CRIAI 35(3):135. [CrossRef]

The Balance Between Expression of Intranuclear NF-??B and Glucocorticoid Receptor in Polymorphonuclear Leukocytes in SIRS Patients
Yasushi Nakamori, Hiroshi Ogura, Taichin Koh, Kieko Fujita, Hiroshi Tanaka, Yuka Sumi, Hideo Hosotsubo, Kazuhisa Yoshiya, Taro Irisawa, Yasuyuki Kuwagata
Journal of Trauma Injury Infection and Critical Care 59(2):308. [CrossRef]

Endogenous regulation of a therapeutic transgene restores homeostasis in arthritic joints
A.V. Miagkov, A.W. Varley, R.S. Munford, S.S. Makarov
J Clin Invest 109(9):1223. [CrossRef]

PDT-associated host response and its role in the therapy outcome
Mladen Korbelik
Lasers Surg Med 38(5):500. [CrossRef]

Activation and Regulation of NFκB during Acute Inflammation
Alex B. Lentsch, Peter A. Ward
cclm 37(3):205. [CrossRef]

INTERLEUKIN-10 AND THE INTERLEUKIN-10 RECEPTOR
Kevin W. Moore, Rene De waal malefyt, Robert L. Coffman, Anne O'garra
annu rev immunol 19(1):683. [CrossRef]

Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat
Amin A. Nanji, Kalle Jokelainen, Amir Rahemtulla, Lili Miao, Franz Fogt, Hiroshi Matsumoto, Steven R. Tahan, Grace L. Su
Hepatol 30(4):934. [CrossRef]

Reduction in the evolution of murine type II collagen-induced arthritis by treatment with rosiglitazone, a ligand of the peroxisome proliferator-activated receptor γ
Salvatore Cuzzocrea, Emanuela Mazzon, Laura Dugo, Nimesh S. A. Patel, Ivana Serraino, Rosanna Di paola, Tiziana Genovese, Domenico Britti, Massimo De maio, Achille P. Caputi
Arthritis Rheum 48(12):3544. [CrossRef]

Regulation of cyclooxygenase-2 expression in human mesangial cells - transcriptional inhibition by IL-13
Manuela Diaz-cazorla, Dolores Perez-sala, Josefa Ros, Wladimiro Jimenez, Manuel Fresno, Santiago Lamas
Eur J Biochem 260(1):268. [CrossRef]

Nuclear Factor-κB- and Glucocorticoid Receptor α- Mediated Mechanisms in the Regulation of Systemic and Pulmonary Inflammation during Sepsis and Acute Respiratory Distress Syndrome
G. Umberto Meduri, Muthiah P. Muthiah, Pierluigi Carratu, Mahmoud Eltorky, George P. Chrousos
12(6):321. [CrossRef]

Pharmacodynamic interactions between recombinant mouse interleukin-10 and prednisolone using a mouse endotoxemia model
Abhijit Chakraborty, Sally Yeung, Nancy A. Pyszczynski, William J. Jusko
J Pharm Sci 94(3):590. [CrossRef]

Intramuscular Gene Transfer of Interleukin-10 Reduces Neutrophil Recruitment and Ameliorates Lung Graft Ischemia-Reperfusion Injury
Benjamin D. Kozower, Samer A. Kanaan, Tsutomu Tagawa, Takashi Suda, Kathleen Grapperhaus, Niccolo Daddi, Erika C. Crouch, Claire M. Doerschuk, G. Alexander Patterson
Am J Transplant 2(9):837. [CrossRef]

Regulation of inflammatory vascular damage
Alex B. Lentsch, Peter A. Ward
J Pathol 190(3):343. [CrossRef]

Nuclear factor-κB inhibitors as sensitizers to anticancer drugs
Chikashi Nakanishi, Masakazu Toi
Nat Rev Cancer 5(4):297. [CrossRef]

Acid-induced Lung Injury
Lilly Madjdpour, Sita Kneller, Christa Booy, Thomas Pasch, Ralph C. Schimmer, Beatrice Beck-schimmer
Anaesthesiology 99(6):1323. [CrossRef]

Suppression of TNF by V antigen ofYersinia spp. involves activated T cells
Annette Schmidt, Martin Röllinghoff, Horst Ulrich Beuscher
Eur J Immunol 29(4):1149. [CrossRef]

Inhibitors of NF-κB signaling: 785 and counting
T D Gilmore, M Herscovitch
Oncogenes 25(51):6887. [CrossRef]

Targeting transcription factors for therapeutic benefit
Paul Brennan, Rossen Donev, Saman Hewamana
Mol Biosyst 4(9):909. [CrossRef]

REGULATION OF LUNG INFLAMMATION IN THE MODEL OF IGG IMMUNE-COMPLEX INJURY
Hongwei Gao, Thomas Neff, Peter A. Ward
Annu Rev Pathol Mech Dis 1(1):215. [CrossRef]

IL-10 attenuates TNF- -induced NF B pathway activation and cardiomyocyte apoptosis
S. Dhingra, A. K. Sharma, R. C. Arora, J. Slezak, P. K. Singal
Cardiovasc Res 82(1):59. [CrossRef]

Systemic delivery of IL-10 by an AAV vector prevents vascular remodeling and end-organ damage in stroke-prone spontaneously hypertensive rat
T Nomoto, T Okada, K Shimazaki, T Yoshioka, M Nonaka-sarukawa, T Ito, K Takeuchi, K-i Katsura, H Mizukami, A Kume
Gene Ther 16(3):383. [CrossRef]

The absence of donor-derived IL-13 exacerbates the severity of acute graft-versus-host disease following allogeneic bone marrow transplantation
Gerhard C. Hildebrandt, Sung W. Choi, Gunnar Mueller, Krystyna M. Olkiewicz, Bethany B. Moore, Kenneth R. Cooke
Pediatric Blood &amp Cancer 50(4):911. [CrossRef]

Biology of TNFα and IL-10, and their imbalance in heart failure
Kuljeet Kaur, Sanjiv Dhingra, Jan Slezak, Anita K. Sharma, Anju Bajaj, Pawan K. Singal
Heart Fail Rev 14(2):113. [CrossRef]