Inflammatory responses of RAW 264.7 macrophages upon exposure to nanoparticles: Role of ROS-NFκB signaling pathway

Abstract

Recent advances in particle-forming chemistries used for developing nanotechnology has not only widened novel applications for nanoscale materials but also has provided significant concern regarding their biological effects. The present study investigates the inflammatory responses of RAW 264.7 mouse macrophages exposed to nanoparticles (NPs, 5 μg/ml) of varied sizes including silver (Ag), aluminum (Al), carbon black (CB), carbon-coated silver (CAg) and gold (Au). A significant increase in IL-6, reactive oxygen species (ROS) generation, nuclear translocation of nuclear factor-kappa B (NF-κB), induction of cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-α) expression was observed in macrophages with maximum response found in cells exposed to Ag NPs followed by Al, CB and CAg. These pro-inflammatory effects of NPs were dependent on size and duration of exposure and comparable to those induced by lipopolysaccharide (LPS), a known inflammatory mediator. Au NPs, on the other hand, induced small but significant inflammatory responses in macrophages upon prolonged exposure. These studies reveal that Ag NPs exhibit higher propensity in inducing inflammation, mediated by ROS and NF-κB signaling pathways and leading to the induction of COX-2, TNF-α and IL-6. However, no such prominent pro-inflammatory responses were observed with Au NPs, suggesting their bio-compatibility.

Keywords::

• Nanoparticles
• inflammation
• ROS
• NF-κB
• cyclooxygenase-2

Acknowledgments

We sincerely acknowledge Dr Steve and Dr Neigh of Nanocomposix (USA), Dr Himabindu and Dr Vivek of JNTU-H (India) for supplying NPs. We also duly acknowledge the support of the Council of Scientific and Industrial Research (CSIR), Govt. of India, for providing a Senior Research Fellowship to Reddy P. Nishanth.

Declaration of interest: This work was supported by research grants (Grant No. FA4869-07-1-0017) from the Asian Office of Aerospace Research and Development (AOARD), USA, and from the Department of Science and Technology (DST) Nano Project (Grant No. IR/S5/IU-01/2006) Govt. of India. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.