Research Papers:

IL-1α and IL-1β-producing macrophages populate lung tumor lesions in mice

Michela Terlizzi, Chiara Colarusso, Ada Popolo, Aldo Pinto and Rosalinda Sorrentino _

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Oncotarget. 2016; 7:58181-58192. https://doi.org/10.18632/oncotarget.11276

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Michela Terlizzi1,2, Chiara Colarusso1, Ada Popolo1, Aldo Pinto1, Rosalinda Sorrentino1

1Department of Pharmacy (DIFARMA), University of Salerno, Salerno, Fisciano, 84084, Italy

2PhD Program in Drug Discovery and Development, University of Salerno, Salerno, Fisciano, 84084, Italy

Correspondence to:

Rosalinda Sorrentino, email: [email protected]

Keywords: NLRP3 inflammasome, lung cancer, IL-1α, IL-1β, tumor-associated macrophages

Abbreviations: Tumor-associated macrophages: TAMs; interleukin-1: IL-1; NLRP3: nod-like receptor 3

Received: March 03, 2016     Accepted: August 09, 2016     Published: August 12, 2016


Macrophages highly populate tumour microenvironment and are referred to as tumor-associated macrophages (TAMs). The inflammasome is a multiprotein complex responsible of IL-1 like cytokines release, which biology has been widely studied by using bone-marrow-derived macrophages to mimic a physiological and/or host defense condition. To understand the role of this complex in lung tumor-associated macrophages (TAMs), we isolated and cultured broncho-alveolar lavage (BAL)-derived cells of lung tumor-bearing mice. The stimulation of lung TAMs with LPS+ATP increased the release of IL-1β. The inhibition of NLRP3 by means of glybenclamide significantly reduced IL-1β release. Similarly, C3H-derived, caspase-1 ko and caspase-11 ko TAMs released significantly reduced levels of IL-1β. Moreover, the stimulation of lung TAMs with the sole LPS induced a significant release of IL-1α, which was significantly reduced after caspase-1 pharmacological inhibition, and in TAMs genetically lacking caspase-1 and caspase-11. The inhibition of calpain I/II by means of MDL28170 did not alter IL-1α release after LPS treatment of lung TAMs. To note, the inoculation of LPS-treated bone marrow-derived macrophages into carcinogen-exposed mice increased lung tumor formation. In contrast, the depletion of TAMs by means of clodronate liposomes reduced lung tumorigenesis, associated to lower in vivo release of IL-1α and IL-1β.

In conclusion, our data imply lung tumor lesions are populated by macrophages which pro-tumor activity is regulated by the activation of the NLRP3 inflammasome that leads to the release of IL-1α and IL-1β in a caspase-11/caspase-1-dependent manner.

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