IgA aggregates stimulate monocyte chemotactic peptide-1 expression in human mesangial cells

It has been observed that mesangial cells (MC) possess receptors for IgG and IgA and that IgG immune complexes activate MC to produce monocyte chemotactic peptide-1 (MCP-1). Therefore, we examined whether IgA immune complexes could stimulate MCP-1 mRNA expression in human MC by using semiquantitative reverse transcription-polymerase chain reaction (PCR). Incubation of MC with IgA or IgG immune aggregates (Agr) effectively enhanced the ratio of PCR products for MCP-1 to glyceraldehyde-3-phosphate dehydrogenase on densitometric results at 24 h. When the monocyte chemotactic activity was examined, MC supernatants produced by IgA or IgG Agr increased the monocyte chemotactic activity. Additional experiments were performed to examine whether protein kinase C (PKC) could regulate the IgA or IgG Agr- induced MCP-1 expression. Phorbol myristate acetate, a PKC activator, increased MCP-1 expression which was inhibited by calphostin C, a PKC inhibitor. One hour of prior incubation of MC with calphostin C could reduce the MCP-1 expression induced by IgA or IgG Agr. These findings demonstrate that IgA as well as IgG immune Agr directly increase MCP-1 expression by MC and it is partly mediated by PKC. The MCP-1 expression induced by IgA or IgG Agr may contribute to monocyte infiltration in the early stage of immune complex glomerulonephritis such as IgA nephropathy or lupus nephritis.