We have previously reported on the discovery and in vitro function of human ML-1 (IL-17F) gene. However, in vivo function of IL-17F remains to be determined. To this end, mouse IL-17F gene was identified and its in vivo function was investigated using a mucosal gene transfer approach.

The full-length mouse IL-17F (mIL-17F) cDNA sequence was identified using both 5'- and 3'-RACE. An expression construct (pcDNAmIL17F) of the mIL-17F coding region sequence was generated. The resulting expression construct (pcDNAmIL17F) was propagated and purified. Groups of mice were administered PBS, a control expression vector, or pcDNAmIL17F by the intratracheal route. 72h after instillation, bronchial alveolar lavage fluid (BALF) samples were analyzed for differential cell counts. Gene expression of pulmonary inflammatory cytokines and C-X-C chemokines was performed by RT-PCR. Airwayhyperreactivity (AHR) to methacholine (Mch) was also measured using whole body plethysmography.

A full-length cDNA with 1178 bp was identified, including a 486-bp coding region sequence. Mucosal transfer of IL-17F gene in Balb/c mice demonstrated a significant increase in the number of BALF neutrophils in mice treated with pcDNAmIL17F. While no significant difference in AHR to Mch was seen in different treatment groups, a significant increase in AHR to Mch in ovalbumin (OVA)-sensitized and challenged mice was noted in mice treated with pcDNAmIL17F when compared to those seen in PBS and mock-treated, OVA-sensitized and challenged mice.

IL-17F induced significant pulmonary neutrophilia in mice, suggesting a role for this new cytokine in neutrophil-associated pulmonary inflammatory responses.