ISA Server

I have an ISA server, today I got calls that users,they can browse, receive mails but they cannot send mails via MS outlook. When I tried to use the Microsoft Outlook on a PC connected to the Internet using a real IP address I could send and receive mails, so everything is Ok in my LAN and the ISP, I checked the ISA server, nothing wrong with it I think, the services are running, I rebooted the ISA server yet still the same, I am not that good in ISA, any help?
NB: I didnt make any changes in the ISA server.