Lead (Pb) as a Factor Initiating and Potentiating Inflammation in Human THP-1 Macrophages.

Emilia Metryka,Patrycja Kupnicka,Dariusz Chlubek,Marta Goschorska,Izabela Gutowska,Patrycja Kapczuk,Donata Simińska,Maciej Tarnowski,Irena Baranowska-Bosiacka

doi:10.3390/ijms21062254

Emilia Metryka, Patrycja Kupnicka + Show 7 more

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https://doi.org/10.3390/ijms21062254

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Abstract

The aim of this study was to assess the influence of lead (Pb) at low concentrations (imitating Pb levels in human blood in chronic environmental exposure to this metal) on interleukin 1β (IL-1β) and interleukin 6 (IL-6) concentrations and the activity and expression of COX-1 and COX-2 in THP-1 macrophages. Macrophages were cultured in vitro in the presence of Pb at concentrations of: 1.25 μg/dL; 2.5 μg/dL; 5 μg/dL; 10 μg/dL. The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range (a dose imitating environmental exposure). Concentrations of 5 μg/dL and 10 μg/dL correspond to the previously permissible PbB concentrations in children or pregnant women, and adults. Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and IL-6), increases expression of COX-1 and COX-2, and increases thromboxane B2 and prostaglandin E2 concentration in macrophages. This clearly suggests that the development of inflammation is associated not only with COX-2 but also with COX-1, which, until recently, had only been attributed constitutive expression. It can be concluded that environmental Pb concentrations are able to activate the monocytes/macrophages similarly to the manner observed during inflammation.

Highlights

The ever-growing awareness of the harmful effects of lead (Pb) on the environment and human health has resulted in a reduction in the use of this metal in the production of fuels, paints, ceramics, and batteries [1]
The first two concentrations of Pb were selected on the basis of our earlier study, which showed that Pb concentration in whole blood (PbB) of young women living in the northern regions of Poland and in the cord blood of their newborn children was within this range
Our results indicate that even low concentrations of Pb cause an increase in production of inflammatory interleukins (IL-1β and interleukin 6 (IL-6)), increases expression of Cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2), and increases thromboxane B2 and prostaglandin E2 concentration in macrophages

Summary

Introduction

The ever-growing awareness of the harmful effects of lead (Pb) on the environment and human health has resulted in a reduction in the use of this metal in the production of fuels, paints, ceramics, and batteries [1]. Pb is still considered to be one of the main substances posing the greatest potential threat to human health. Chronic exposure to low Pb concentrations is a serious public health problem in large urban agglomerations and industrial areas [3,4,5]. Inhabitants of these areas are constantly exposed to low doses of Pb, which may lead to cognitive impairment during the development and disorders in neurobehavioral functioning, for example, aggression [6,7,8,9]. In low environmental concentrations, Pb does not cause visible damage to the body s main immune cells, it may adversely affect their function [10,11,12,13,14]

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