0973: Effects of a Novel Hybrid Protein Based on S100 on Macrophage Polarization and Its Therapeutic Efficacy in a Bleomycin-Induced Systemic Sclerosis Mouse Model.

Background/Purpose: S100 proteins are involved in the inflammatory responses of autoimmune diseases. We previously showed that S100 proteins regulate macrophage function via CD68. Based on this, we developed a novel human hybrid protein, human MIKO-1 (hMIKO-1), derived from the primary structure of human S100. This study aimed to investigate its effects on macrophage polarization and its therapeutic potential in a systemic sclerosis (SSc) mouse model with interstitial lung disease (ILD).

Methods: Murine macrophages were co-cultured with hMIKO-1 to evaluate its effect on macrophage polarization. In vivo, female C57BL/6 mice were injected subcutaneously with bleomycin (200 μg/mouse, every other day) to induce skin and lung lesions resembling SSc-associated ILD (SSc-ILD). Mice were divided into three groups: sham control, disease control (BLM + vehicle), and treatment (BLM + hMIKO-1). After four weeks, skin and lung tissues were collected and assessed histologically.

Results: hMIKO-1 significantly inhibited M2 polarization of murine macrophages in vitro. In vivo, lung fibrosis scores were significantly lower in the hMIKO-1-treated group compared to the disease control group, while no significant difference was found in skin fibrosis. F4/80-positive macrophages in both skin and lung tissues were significantly reduced in the hMIKO-1 group. Notably, hMIKO-1 accumulation differed between lungs and skin.

Conclusion: hMIKO-1 attenuated inflammation and fibrosis in the lungs of SSc-ILD model mice. Its limited effect in the skin may be due to differences in tissue accumulation. hMIKO-1 may serve as a potential targeted therapy for SSc-associated ILD.