Sulforaphane inhibits de novo synthesis of IL-8 and MCP-1 in human epithelial cells generated by cigarette smoke extract

J Immunotoxicol. 2011 Jun;8(2):150-8. doi: 10.3109/1547691X.2011.558529. Epub 2011 Mar 14.


Chronic obstructive pulmonary disease (COPD) is currently the fifth leading cause of death worldwide. Exposure to cigarette smoke (CS) is the primary factor associated with the COPD development. CS activates epithelial cells to secrete chemokines such as interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) that recruit neutrophils and macrophages to the lung. These inflammatory cells then release additional chemokines and cytokines leading to chronic inflammation that initiates apoptosis in epithelial and endothelial cells and destruction of alveolar structure. Pulmonary epithelium responds to oxidative stress mediated by CS through activating NRF2-dependent pathways, leading to an increased expression of antioxidant and cytoprotective enzymes thereby providing a protective response against CS-induced lung injury. We hypothesized that activating NRF2-dependent cytoprotective gene expression with sulforaphane (SFN) affords protection against CS-induced lung damage by inhibiting chemokine production. Results indicate that in the human BEAS-2B epithelial cell line, 5 μM SFN activated NRF2-dependent gene expression by triggering the translocation of NRF2 to the nucleus and significantly increased the expression of NRF2-dependent genes such as NADPH quinone oxidoreductase-1, heme oxygenase-1, and glutamate cysteine ligase modulatory subunit. Cigarette smoke extract (CSE) exposure of BEAS-2B cells significantly increased production of both IL-8 and MCP-1. Production of both chemokines was significantly reduced with SFN given prior to CSE; SFN inhibited IL-8 and MCP-1 gene expression at the transcription level. Our results indicate that activating NRF2 pathways with SFN inhibits CSE-induced chemokine production in human epithelial cells. However, the mechanism by which the production of chemokines is inhibited through SFN still remains to be elucidated. SFN may enhance NRF2 transcriptional activity resulting in the inhibition of proinflammatory pathways such as NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticarcinogenic Agents / adverse effects*
  • Anticarcinogenic Agents / pharmacokinetics
  • Cell Line
  • Chemokine CCL2 / biosynthesis
  • Chemokine CCL2 / immunology*
  • Epithelial Cells / immunology*
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / immunology
  • Glutamate-Cysteine Ligase / immunology
  • Glutamate-Cysteine Ligase / metabolism
  • Heme Oxygenase-1 / immunology
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / immunology*
  • Isothiocyanates
  • NAD(P)H Dehydrogenase (Quinone) / immunology
  • NAD(P)H Dehydrogenase (Quinone) / metabolism
  • NF-E2-Related Factor 2 / immunology
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Pulmonary Alveoli / immunology
  • Pulmonary Alveoli / metabolism
  • Pulmonary Alveoli / pathology
  • Pulmonary Disease, Chronic Obstructive / etiology
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Smoke / adverse effects
  • Smoking / adverse effects
  • Thiocyanates / adverse effects*
  • Thiocyanates / pharmacology


  • Anticarcinogenic Agents
  • CCL2 protein, human
  • CXCL8 protein, human
  • Chemokine CCL2
  • Interleukin-8
  • Isothiocyanates
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • Smoke
  • Thiocyanates
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • Glutamate-Cysteine Ligase
  • sulforafan